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Yuji Owada

Section

Graduate School of Medicine

Job title

Professor

Degree

researchmap

https://researchmap.jp/owada

J-GLOBAL ID

201801004432618068

e-Rad No.

20292211

Research History 5

2015 - Present

Tohoku University
2006 - 2014

Yamaguchi University
2002 - 2006

Tohoku University
2000 - 2002

Tohoku University
1997 - 1999

Tohoku University

Education 2

Tohoku University　Graduate School of Medicine

- 1997/03
Tohoku University　Faculty of Medicine　School of Medicine

- 1989/03

Professional Memberships 6

米国神経科学会
THE JAPANESE ASSOCIATION OF ANATOMISTS
日本神経科学会
JAPAN BRAIN SCIENCE SOCIETY
THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY

︎Show all ︎Show first 5

Research Interests 6

Lipid
栄養と免疫機能連関
栄養と神経機能連関
脂肪酸
FABP
アストロサイト

Research Areas 5

Life sciences / Sports science /
Other / Other / Laboratory medicine
Life sciences / Neuroanatomy and physiology /
Humanities & social sciences / Home economics, lifestyle science /
Life sciences / Anatomy /

Awards 3

学術奨励賞

2007　宇部興産学術振興財団　ＦＡＢＰ分子の神経系における機能調節機構の解析
奨励賞

1999　東北医学会　脳における脂肪酸結合タンパク質の発現と機能
奨励賞

1999　日本解剖学会　脂肪酸結合蛋白質の組織発現・機能解析

Papers 220

Maternal granulocyte colony-stimulating factor alters synaptic maturation and social behaviors in offspring. International-journal Peer-reviewed

Hinako Kirikae, Karina Kimura, Jinghang Fu, Zhengkang Sun, Hongbo Wang, Haruka Shibuya, Yoshiyuki Kasahara, Hirofumi Miyazaki, Yui Yamamoto, Mai Sakai, Zhiqian Yu, Shohei Ochi, Fumito Naganuma, Takeo Yoshikawa, Takashi Namba, Noriko Osumi, Hiroaki Tomita, Yuji Owada, Motoko Maekawa

Brain, behavior, and immunity　106534-106534　2026/03/11

DOI： 10.1016/j.bbi.2026.106534 　

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Neurodevelopmental disorders, including autism spectrum disorder (ASD), arise from complex interactions between genetic and environmental factors. Maternal immune activation (MIA) is a key environmental risk factor that disrupts embryonic neurodevelopment, primarily through inflammatory cytokines. However, the contribution of non-inflammatory cytokines, particularly hematopoietic growth factors, remains poorly understood. Here, we identified granulocyte colony-stimulating factor (G-CSF) as a candidate mediator of MIA-induced neurodevelopmental alterations. Polyinosinic:polycytidylic acid [poly(I:C)] administration to pregnant dams at embryonic day 12.5 (E12.5) significantly increased G-CSF levels in both maternal plasma and embryonic tissue. To assess its contribution to neurodevelopmental alterations, we administered human G-CSF (hG-CSF) to pregnant dams at E12.5. At the structural level, male offspring exposed to prenatal hG-CSF showed increased dendritic spine density and a higher proportion of immature spines in the medial prefrontal cortex. Behaviorally, both male and female offspring exhibited altered social preference. Bulk RNA-seq analysis of the prefrontal cortex revealed altered enrichment of pathways related to synapse organization, translation, and mitochondrial function in both sexes, with opposite directions of enrichment in males and females. In vitro, G-CSF attenuated synapse maturation and enhanced microglial phagocytic activity. These findings suggest that G-CSF may contribute to MIA-associated neurodevelopmental alterations, potentially through disrupted synapse maturation and microglial function. Our results highlight a hematopoietic pathway that may contribute to mechanisms underlying neurodevelopmental disorders, including ASD.
Perichondrium origin of pericyte‐septoclast lineage in endochondral bone development

Yasuhiko Bando, Arata Nagasaka, Miyuki Toda‐Fujii, Yuji Owada, Osamu Amano

Journal of Anatomy　2025/11/30
Publisher: Wiley
DOI： 10.1111/joa.70081 　

ISSN： 0021-8782

eISSN： 1469-7580

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Abstract During endochondral bone development, pericytes differentiate into septoclasts, a mononuclear cartilage‐resorbing cells, and contribute to the forming primary ossification center. To clarify the origin of the pericyte‐septoclast lineage, the present study investigated the chronological localization of pericytes, septoclasts, and perichondrial cells during the early developmental stage of mouse tibiae using specific histochemical markers: platelet‐derived growth factor receptor beta (PDGFRβ) for pericytes, epidermal‐type fatty acid‐binding protein (E‐FABP, FABP5) for septoclasts, distal‐less homeobox 5 (DLX5) for perichondrial cells, and von Kossa method and periostin for the periosteum. Before blood vessel invasion and septoclast appearance, PDGFRβ and DLX5 were commonly expressed in pericytes and in the cells of the outer layer of the perichondrium (OPC). Moreover, DLX5 positive OPC cells projected inward and were continuous with pericytes in the mid‐portion of the cartilaginous templates. After the onset of blood vessel invasion and septoclast appearance, DLX5 was localized in both pericytes and septoclasts, suggesting that pericytes originated from OPC cells and differentiated into DLX5‐expressing septoclasts. Based on the localization of von Kossa‐positive calcified substrates and periostin immunoreactivity, OPC cells were transformed into the periosteum. Immunoreactivity of PDGFRβ, which mediates pericyte migration or recruitment, was relatively weak in the perichondrium compared to that observed before blood vessel invasion. In conclusion, the present results suggest that the pericyte‐septoclast lineage originates from perichondrial cells during the initial developmental stage of endochondral bone formation.
ETS1 promotes the expression of Ctsb and Mmp13 during the differentiation of septoclasts from pericytes. International-journal

Yasuhiko Bando, Kenjiro Bandow, Koji Sakiyama, Arata Nagasaka, Kaito Suzuki, Miyuki Toda-Fujii, Yuji Owada, Osamu Amano

Cell and tissue research　401　(1)　29-42　2025/07

DOI： 10.1007/s00441-025-03979-x 　

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Septoclasts (SCs), which express both fatty acid-binding protein 5 and platelet-derived growth factor beta, are mononuclear cartilage-resorbing cells predominantly located at the chondro-osseous junction of the growth plate (GP). These cells originate from pericytes (PCs). Cathepsin B (CTSB) and matrix metalloproteinase-13 (MMP13), expressed in SCs, participate in the degradation of collagen and other cartilage matrices. This study aimed to investigate the involvement of the ETS proto-oncogene 1 (ETS1) in the transcription of Ctsb and Mmp13 during the differentiation of SCs from PCs. ETS1 was localized in SCs and a small number of PCs during development and postnatal stages. Upregulation of Ets1, Mmp13, Ctsb, and the Ets1-related genes, specificity protein 1 (Sp-1), jun proto-oncogene (c-Jun), and cAMP response element-binding protein-binding protein (Crebbp) in SCs compared with those in PCs was shown by RNA-seq analysis of samples isolated from the tibiae of 3-week-old postnatal mice. The Ets1-related proteins were localized ubiquitously in SCs and PCs in the GP. In primary SC cultures, the expression levels of Ctsb and Mmp13 were significantly reduced following treatment with Ets1 siRNA. Thus, our results revealed that ETS1 promoted the expression of Ctsb and Mmp13 in SCs during the differentiation of SCs from PCs.
High-Fat Diet-Induced Excessive Accumulation of Cerebral Cholesterol Esters and Microglial Dysfunction Exacerbate Alzheimer's Disease Pathology in APPNL-G-F mice. International-journal

Shuhan Yang, Hirofumi Miyazaki, Tunyanat Wannakul, Eiko Amo, Takaomi Saido, Takashi Saito, Hiroki Sasaguri, Motoko Maekawa, Yuji Owada

Molecular neurobiology　2025/05/17

DOI： 10.1007/s12035-025-05052-8 　

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Epidemiological studies have identified high-fat diet (HFD)-induced obesity as a risk factor for Alzheimer's disease (AD), yet the underlying molecular mechanisms remain inadequately elucidated. Microglia, the brain's innate immune cells, are pivotal in AD brain by engulfing β-amyloid (Aβ) peptides and compacting poorly consolidated Aβ plaques. Microglia are highly susceptible to the metabolic milieu; however, it is unclear how long-term HFD alters the lipid environment and influences microglial phenotype in AD brains. In this study, APPNL-G-F knock-in AD model mice were fed an HFD for 9-27 weeks and subsequently analyzed for Aβ pathology and microglial function. Our findings indicated that HFD intake accelerated Aβ deposition, attenuated the recruitment of microglia to the plaques and impaired their phagocytic activity, while also promoting the accumulation of intracellular lipid droplets (LDs). Lipidomic analyses revealed that HFD, in synergy with AD pathology, increased the proportion of cholesterol esters in the cerebral cortex. In vitro, oleic acid-a major HFD constituent-similarly diminished the phagocytic capacity of MG6 microglia and induced LDs accumulation, along with downregulation of gene sets of cholesterol efflux, phagocytosis and engulfment. Overall, these findings implied that HFD-induced perturbation in brain cholesterol homeostasis may compromise microglial activation and expedite AD progression in APPNL-G-F mice.
Loss of fatty acid-binding protein 7 promotes B16F10 melanoma metastasis. International-journal

Tunyanat Wannakul, Hirofumi Miyazaki, Motoko Maekawa, Yoshiteru Kagawa, Yui Yamamoto, Yuji Owada

Scientific reports　15　(1)　10495-10495　2025/03/26

DOI： 10.1038/s41598-024-80874-5 　

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Melanoma possesses the characteristic phenotypic plasticity, enhancing its metastatic formation and drug resistance. Lipid and fatty acid metabolism are usually altered to support melanoma progression and can be targeted for therapeutic development. Fatty acid binding protein 7 (FABP7) is highly expressed in melanomas and is shown to support its proliferation, migration, and invasion, but the mechanisms remain unclear. Our study aimed to link FABP7 to lipid metabolism and phenotypic shift in melanomas. We established the Fabp7-knockout (KO) B16F10 melanoma cells, which showed an enhanced invasion through matrix-coated membrane, without significant change in proliferation. Similar outcomes were obtained when using RNA interference targeting FABP7. Fabp7-KO cells injected into mice exhibited slower primary tumor growth, but formed higher metastatic foci count in the lungs. We also discovered a higher saturation in overall lipids, phosphatidylcholines, and triacylglycerols. We observed transcriptional shifts toward the invasive MITFLow/AXLHigh phenotype, with upregulation of transforming growth factor-beta (TGF-β) receptor mRNAs. In conclusion, FABP7 may help balancing lipid saturation and maintain the proliferative state of melanomas, mitigating invasiveness and metastatic formation.
Effects of pharmacological inhibition of FABP4 during gestation and lactation on offspring neurodevelopment and behavior. International-journal

Sun Zhengkang, Hinako Kirikae, He Xiaofeng, Fumiko Yoshimachi, Minori Ikuta, Tetsuo Ohnishi, Yui Yamamoto, Hirofumi Miyazaki, Yoshiyuki Kasahara, Mai Sakai, Zhiqian Yu, Noriko Osumi, Hiroaki Tomita, Yuji Owada, Motoko Maekawa

Neuroscience letters　853　138199-138199　2025/03/14

DOI： 10.1016/j.neulet.2025.138199 　

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Fatty acid-binding protein 4 (FABP4), a key regulator of lipid metabolism and inflammation, has been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). This study investigated the effects of FABP4 inhibition during gestation and lactation on offspring neurodevelopment using the selective FABP4 inhibitor BMS309403. Female mice received BMS309403 (15 mg/kg) via oral gavage from two weeks before mating to postnatal day 28 (P28). Administration of BMS309403 to mouse dams resulted in autism-like phenotypes in male offspring (behavioral tests: n = 7-10 per group; spine analysis: 6 mice per group, n = 26-38 dendrites per group), characterized by increased dendritic spine density in the prefrontal cortex, impaired vocal communication, increased repetitive behaviors, and depression-like symptoms. Fatty acid analysis (n = 4-6 per group) revealed significant alterations in maternal and fetal lipid profiles, including elevated arachidonic acid levels in maternal plasma and increased n6PUFAs in the fetal brain, suggesting a pro-inflammatory lipid environment. Principal component analysis demonstrated distinct clustering of lipid profiles between control and BMS309403-treated groups. Cytokine analysis (n = 6 per group) indicated reductions in IL-10 and IL-12(p40) in maternal plasma and decreased TNFα in the fetal plasma, suggesting dysregulation in systemic inflammatory signaling. These findings suggest that FABP4 inhibition during the perinatal period perturbs lipid metabolism and may influence neurodevelopment through systemic metabolic changes. Although the direct effects of BMS309403 on the fetal brain cannot be excluded, alteration in maternal metabolism and placental function may have contributed to the observed neurodevelopmental changes in offspring.
Gene Expression Profiling in the Cortex of Fabp4 Knockout Mice

Hinako Kirikae, Xiaofeng He, Tetsuo Ohnishi, Hirofumi Miyazaki, Takeo Yoshikawa, Yuji Owada, Motoko Maekawa

Neuropsychopharmacology Reports　45　(1)　2025/02/08
Publisher: Wiley
DOI： 10.1002/npr2.70006 　

ISSN： 2574-173X

eISSN： 2574-173X

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ABSTRACT Aims Fatty acid binding protein 4, adipocyte (Fabp4), is well known for its role in peripheral lipid metabolism, but its potential role in brain function remains largely unexplored. This study aimed to investigate Fabp4 expression in the adult mouse brain and explore gene expression changes in Fabp4 knockout (KO) mice to assess its potential impact on brain function. Methods We conducted in situ hybridization to assess Fabp4 expression in key brain regions of adult mice. In parallel, differential gene expression analysis using RNA‐seq was conducted in the prefrontal cortex of Fabp4 KO mice to identify genes affected by Fabp4 deficiency. Results No Fabp4 expression was detected in the brains of mice, suggesting a lack of direct involvement in the central nervous system. However, Fabp4 KO mice exhibited significant changes in gene expression in the brain, with 31 genes upregulated and 30 downregulated. Downregulated genes were linked to histone methylation and metabolic processes, while upregulated ones were associated with synaptic organization. Conclusion Although Fabp4 is not expressed in the brain, its deficiency leads to substantial changes in gene expression, likely mediated by peripheral metabolic pathways and epigenetic regulation. These changes may explain the previously observed autism‐like behaviors and increased dendritic spine density in Fabp4 KO mice. This study sheds light on the role of systemic lipid metabolism in neurodevelopmental disorders such as autism spectrum disorder (ASD) and highlights epigenetic mechanisms as potential mediators of these effects.
FABP7 in Hepatic Macrophages Promotes Fibroblast Activation and CD4+ T-Cell Migration by Regulating M2 Polarization During Liver Fibrosis. International-journal

Hirofumi Miyazaki, Tunyanat Wannakul, Shuhan Yang, Dandan Yang, Ayano Karasawa, Ai Shishido, Ruizhu Cao, Yui Yamamoto, Yoshiteru Kagawa, Shuhei Kobayashi, Masaki Ogata, Motoko Maekawa, Yuji Owada

Journal of immunology research　2025　6987981-6987981　2025

DOI： 10.1155/jimr/6987981 　

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Hepatic macrophages respond to various microenvironmental signals and play a central role in maintaining hepatic homeostasis, dysregulation of which leads to various liver diseases. Fatty acid-binding protein 7 (FABP7), an intracellular lipid chaperone for polyunsaturated fatty acids (PUFAs), is highly expressed in liver macrophages. However, the mechanisms by which FABP7 regulates hepatic macrophage activation remain unclear. Therefore, we aimed to elucidate the mechanisms underlying the effects of FABP7 on the functions of hepatic macrophages in metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis models. In this study, we found that FABP7-deficient macrophages exhibited impaired M2 polarization, which reduced the fibrotic response of myofibroblasts and CD4+ T-cell infiltration into the liver tissues in a carbon tetrachloride (CCl4)-induced hepatic fibrosis model. In vitro, FABP7-deficient macrophages exhibited decreased levels of peroxisome proliferator-activated receptor (PPAR)-γ and its target genes, including C-C motif chemokine ligand (CCL)-17 and transforming growth factor-β (TGF-β), compared to the wild-type (WT) macrophages post-interleukin (IL)-4 stimulation. However, these effects were inhibited by a PPARγ inhibitor. IL-4-stimulated WT macrophages also promoted CD4+ T-cell migration and hepatic fibroblast (TWNT-1 hepatic stellate cell [HSC]) activation, indicated by increased mRNA levels of actin alpha 2, smooth muscle (ACTA2), and collagen type I alpha 1 (COL1A1); however, these effects were inhibited in FABP7-deficient macrophages. Overall, FABP7 in hepatic macrophages modulated the crosstalk between hepatic fibroblasts and T cells by regulating M2 polarization. Therefore, regulation of hepatic macrophage function by FABP7 is a potential therapeutic target for liver fibrosis.
Fatty acid preference for beta‐oxidation in mitochondria of murine cultured astrocytes

Laarni Grace Corales, Hitoshi Inada, Yuji Owada, Noriko Osumi

Genes to Cells　2024/07/04
Publisher: Wiley
DOI： 10.1111/gtc.13144 　

ISSN： 1356-9597

eISSN： 1365-2443

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Abstract The brain utilizes glucose as a primary energy substrate but also fatty acids for the β‐oxidation in mitochondria. The β‐oxidation is reported to occur mainly in astrocytes, but its capacity and efficacy against different fatty acids remain unknown. Here, we show the fatty acid preference for the β‐oxidation in mitochondria of murine cultured astrocytes. Fatty acid oxidation assay using an extracellular flux analyzer showed that saturated or monosaturated fatty acids, palmitic acid and oleic acid, are preferred substrates over polyunsaturated fatty acids like arachidonic acid and docosahexaenoic acid. We also report that fatty acid binding proteins expressed in the astrocytes contribute less to fatty acid transport to mitochondria for β‐oxidation. Our results could give insight into understanding energy metabolism through fatty acid consumption in the brain.
Polyunsaturated fatty acids-induced ferroptosis suppresses pancreatic cancer growth.

Suda A, Umaru BA, Yamamoto Y, Shima H, Saiki Y, Pan Y, Jin L, Sun J, Low YLC, Suzuki C, Abe T, Igarashi K, Furukawa T, Owada Y, Kagawa Y

Scientific reports　2024/02/22

DOI： 10.1038/s41598-024-55050-4 　

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Despite recent advances in science and medical technology, pancreatic cancer remains associated with high mortality rates due to aggressive growth and no early clinical sign as well as the unique resistance to anti-cancer chemotherapy. Current numerous investigations have suggested that ferroptosis, which is a programed cell death driven by lipid oxidation, is an attractive therapeutic in different tumor types including pancreatic cancer. Here, we first demonstrated that linoleic acid (LA) and α-linolenic acid (αLA) induced cell death with necroptotic morphological change in MIA-Paca2 and Suit 2 cell lines. LA and αLA increased lipid peroxidation and phosphorylation of RIP3 and MLKL in pancreatic cancers, which were negated by ferroptosis inhibitor, ferrostatin-1, restoring back to BSA control levels. Similarly, intraperitoneal administration of LA and αLA suppresses the growth of subcutaneously transplanted Suit-2 cells and ameliorated the decreased survival rate of tumor bearing mice, while co-administration of ferrostatin-1 with LA and αLA negated the anti-cancer effect. We also demonstrated that LA and αLA partially showed ferroptotic effects on the gemcitabine-resistant-PK cells, although its effect was exerted late compared to treatment on normal-PK cells. In addition, the trial to validate the importance of double bonds in PUFAs in ferroptosis revealed that AA and EPA had a marked effect of ferroptosis on pancreatic cancer cells, but DHA showed mild suppression of cancer proliferation. Furthermore, treatment in other tumor cell lines revealed different sensitivity of PUFA-induced ferroptosis; e.g., EPA induced a ferroptotic effect on colorectal adenocarcinoma, but LA or αLA did not. Collectively, these data suggest that PUFAs can have a potential to exert an anti-cancer effect via ferroptosis in both normal and gemcitabine-resistant pancreatic cancer.
Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice. International-journal

Jun Suzuki, Tomotaka Hemmi, Masamitsu Maekawa, Masahiro Watanabe, Hitoshi Inada, Hiroyuki Ikushima, Tetsuya Oishi, Ryoukichi Ikeda, Yohei Honkura, Yoshiteru Kagawa, Tetsuaki Kawase, Nariyasu Mano, Yuji Owada, Noriko Osumi, Yukio Katori

Scientific reports　13　(1)　21494-21494　2023/12/06

DOI： 10.1038/s41598-023-48702-4 　

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Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.
Curcumin analog GO-Y030 inhibits tumor metastasis and glycolysis

Takashi MaruYama, Hirofumi Miyazaki, Taishi Komori, Shion Osana, Hiroyuki Shibata, Yuji Owada, Shuhei Kobayashi

The Journal of Biochemistry　2023/09/01
Publisher: Oxford University Press (OUP)
DOI： 10.1093/jb/mvad066 　

ISSN： 0021-924X

eISSN： 1756-2651

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Abstract Tumor metastasis is one of the worst prognostic features of cancer. Although metastasis is a major cause of cancer-related deaths, an effective treatment has not yet been established. Here, we explore the anti-tumor effects of GO-Y030, a curcumin analog, via various mechanisms using a mouse model. GO-Y030 treatment of B16-F10 melanoma cells inhibited TGF-β expression and glycolysis. The invasion assay results showed almost complete invasion inhibition following GO-Y030 treatment. Mouse experiments demonstrated that GO-Y030 administration inhibited lung tumor metastasis without affecting vascular endothelial cells. Consistent with this result, GO-Y030 treatment led to the downregulation of MMP2 and VEGFα, inhibiting tumor invasion and metastasis. The silencing of eIF4B, a downstream molecule of S6, attenuated MMP2 expression. Our study demonstrates the novel efficacy of GO-Y030 in inhibiting tumor metastasis by regulating metastasis-associated gene expression via inhibiting dual access, glycolytic, and TGF-β pathways.
Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Tomotaka Hemmi, Jun Suzuki, Yoshiteru Kagawa, Yohei Honkura, Ryoukichi Ikeda, Ken Hashimoto, Chitose Suzuki, Tetsuaki Kawase, Takaaki Abe, Yuji Owada, Yukio Katori

The Tohoku journal of experimental medicine　2023/04/20

DOI： 10.1620/tjem.2023.J031 　
Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation and Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose Peer-reviewed

MaruYama T, Miyazaki H, Lim YJ, Gu J, Ishikawa M, Yoshida T, Chen W, Owada Y, Shibata H

Frontiers in Immunology (T Cell Biology)　In press　2023/01/11

DOI： 10.3389/fimmu.2023.1049713 　
Microglia with fatty acid‐binding protein 5 deficiency exhibit proinflammatory phenotype contributing to neuroinflammation

Yoshiteru Kagawa, Liang Jin, Jiaqi Sun, Joseph Nicolazzo, Yuji Owada, Yijun Pan

Alzheimer's & Dementia　18　(S4)　2022/12/20
Publisher: Wiley
DOI： 10.1002/alz.069149 　

ISSN： 1552-5260

eISSN： 1552-5279
Oleic acid‐bound <scp>FABP7</scp> drives glioma cell proliferation through regulation of nuclear lipid droplet formation

Banlanjo Abdulaziz Umaru, Yoshiteru Kagawa, Yuki Ohsaki, Yijun Pan, Chuck T. Chen, Daniel K. Chen, Toshiaki Abe, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Motoko Maekawa, Yui Yamamoto, Tunyanat Wannakul, Shuhan Yang, Richard P. Bazinet, Yuji Owada

The FEBS Journal　290　(7)　1798-1821　2022/11/03
Publisher: Wiley
DOI： 10.1111/febs.16672 　

ISSN： 1742-464X

eISSN： 1742-4658
Unpredictable chronic mild stress differentially impacts resting brain glucose metabolism in fatty acid-binding protein 7 deficient mice. International-journal

John Hamilton, Nicole Roeder, Brittany Richardson, Nikki Hammond, Munawwar Sajjad, Rutao Yao, Yuji Owada, Yoshiteru Kagawa, Panayotis K Thanos

Psychiatry research. Neuroimaging　323　111486-111486　2022/07

DOI： 10.1016/j.pscychresns.2022.111486 　

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Fatty acid-binding proteins (FABPs) are intracellular chaperone proteins involved in the trafficking of n-3 polyunsaturated fatty acids and endocannabinoids. Inhibiting two of the main FABP subtypes found in the brain (FABP5 and FABP7) hinders endocannabinoid uptake and hydrolysis. Prior data indicates that cannabinoid receptor stimulation can ameliorate the consequences associated with chronic stress. To this end, FABP expression may play a similar role in response to stressful conditions. Male C57BL/6 J (WT) and FABP7 knockout (KO) mice were assigned to either a non-stress cohort or an unpredictable chronic mild stress (UCMS) cohort for a period of 4 weeks. Immediately after 4 weeks, mice were injected with [18F]2-fluoro-2-deoxy-d-glucose (FDG) and scanned using micro positron emission tomography (mPET) to examine brain glucose metabolism (BGluM). WT mice exposed to UCMS showed reduced BGluM in striatal, cortical, and hypothalamic regions and showed increased BGluM in the hippocampus, thalamus, periaqueductal gray, superior colliculi, inferior colliculi, and cerebellum. In contrast, there were limited effects of UCMS on BGluM in FABP7 KO mice, with a reduction in the thalamus, periaqueductal gray, and superior colliculi. These findings provide novel insight into FABP7 expression and indicate this gene to play an important role in response to aversive stimuli.
Genetics of bipolar disorder: insights into its complex architecture and biology from common and rare variants. International-journal

Tomonori Hara, Yuji Owada, Atsushi Takata

Journal of human genetics　2022/05/26

DOI： 10.1038/s10038-022-01046-9 　

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Bipolar disorder (BD) is a common mental disorder characterized by recurrent mood episodes, which causes major socioeconomic burdens globally. Though its disease pathogenesis is largely unknown, the high heritability of BD indicates strong contributions from genetic factors. In this review, we summarize the recent achievements in the genetics of BD, particularly those from genome-wide association study (GWAS) of common variants and next-generation sequencing analysis of rare variants. These include the identification of dozens of robust disease-associated loci, deepening of our understanding of the biology of BD, objective description of correlations with other psychiatric disorders and behavioral traits, formulation of methods for predicting disease risk and drug response, and the discovery of a single gene associated with bipolar disorder and schizophrenia spectrum with a large effect size. On the other hand, the findings to date have not yet made a clear contribution to the improvement of clinical psychiatry of BD. We overview the remaining challenges as well as possible paths to resolve them, referring to studies of other major neuropsychiatric disorders.
Environmental enrichment sex-dependently rescues memory impairment in FABP5 KO mice not mediated by brain-derived neurotrophic factor. International-journal

Matthew Marion, John Hamilton, Brittany Richardson, Nicole Roeder, Antonio Figueiredo, Amanda Nubelo, Eleftherios Hetelekides, Samantha Penman, Yuji Owada, Yoshiteru Kagawa, Panayotis K Thanos

Behavioural brain research　425　113814-113814　2022/05/03

DOI： 10.1016/j.bbr.2022.113814 　

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Fatty acid-binding proteins (FABPs) are intracellular carriers of bioactive lipids and play a role in the trafficking of endocannabinoids as well as polyunsaturated fatty acids. Mice lacking the FABP5 gene have memory impairments. Environmental enrichment is a potent manipulation known to rescue or improve memory performance. The extent to which the memory impairments in FABP5 knockout (KO) mice can be rescued or improved through environmental conditions remains to be understood. To address this, we raised wild type (WT) and FABP5 KO mice in either socially isolated or environmental enrichment conditions during adolescence. Once in adulthood, mice were tested for Novel Object Recognition (NOR), T-maze, and Morris Water Maze (MWM) to evaluate memory performance. Mice were then euthanized to assess hippocampal brain-derived neurotrophic factor (BDNF) concentrations. MWM results showed that male FABP5 KO mice performed worse compared to WT counterparts. Male and female mice raised in an enriched environment improved performance regardless of genotype. Results on the NOR test showed that male FABP5 KO mice displayed lower object recognition compared to WT counterparts across both environments. No differences of genotype or environment were seen in female mice. T-maze findings revealed impaired performance in socially isolated FABP5 KO mice. Adolescent environmental enrichment rescued this deficit in male, but not female, FABP5 KO mice. Lastly, environmental enrichment increased hippocampal BDNF levels in male WT mice only. Our results corroborate the previously observed role of the FABP5 gene on memory performance and identify an important interaction with the environment during adolescence.
Spatial and chronological localization of septoclasts in the mouse Meckel's cartilage. International-journal

Hide Sakashita, Yasuhiko Bando, Arata Nagasaka, Koji Sakiyama, Go Onozawa, Fuyoko Taira, Yudai Ogasawara, Yuji Owada, Hideaki Sakashita, Osamu Amano

Histochemistry and cell biology　157　(5)　569-580　2022/05

DOI： 10.1007/s00418-022-02085-1 　

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Meckel's cartilage (MC) in the first branchial arch of mammals is a transient structure that disappears before birth, except for the most anterior and posterior portions. Recent studies reported that some congenital abnormalities in craniofacial regions are linked with the persistence or dysplasia of MC. However, the mechanisms underlying the resorption of MC have not been elucidated. Cartilage resorption in endochondral ossification is performed by multinuclear osteoclasts/chondroclasts as well as mononuclear septoclasts, which were newly added to the list of cartilage phagocytes. Septoclasts located exclusively at the chondro-osseous junction of the growth plate resorb the uncalcified cartilage matrix. We hypothesized that septoclasts participate in the resorption of MC and attempted to clarify the localization and roles of septoclasts in MC of mouse using a specific immunohistochemistry marker, epidermal type-fatty acid-binding protein (E-FABP/FABP5). E-FABP-immunopositive septoclasts were detected for the first time at the beginning of MC resorption and localized along the resorption surface. Septoclasts of MC in embryonic mice possessed several processes that elongated toward the uncalcified cartilage matrix, expressed cathepsin B, and exhibited characteristic pericapillary localization. Additionally, they localized between hypertrophied cartilage and osteoclasts/chondroclasts in the resorption surface. Confocal laser-scanning microscopy revealed a decrease in the numbers of septoclasts and their processes with the progression of MC disappearance before birth. The present study showed that E-FABP-immunopositive septoclasts participated in the disappearance of MC through the resorption of the uncalcified cartilage matrix and that they have different roles from osteoclasts/chondroclasts.
Septoclasts expressing epidermal fatty acid-binding protein (E-FABP, FABP5) in endochondral ossification. International-journal

Yasuhiko Bando, Hide Sakashita, Arata Nagasaka, Koji Sakiyama, Nobuko Tokuda, Shoichi Iseki, Yuji Owada, Osamu Amano

Journal of oral biosciences　64　(1)　18-25　2022/03

DOI： 10.1016/j.job.2021.12.003 　

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BACKGROUND: Long-chain fatty acids (LCFAs) and retinoic acid (RA) are abundant in the growth plates (GPs) of long bones; however, their roles have not been elucidated. We observed that epidermal fatty acid-binding protein (E-FABP/FABP5) with a high affinity for both LCFAs and RA is exclusively expressed in the septoclasts located at the chondro-osseous junction (COJ) of the GP. HIGHLIGHTS: E-FABP expressed in septoclasts is involved in both LCFA metabolism and RA signaling as an intracellular transporter of both LCFAs and RA. Septoclasts with shortened cytoplasmic processes are associated with cartilage resorptive activity downregulation because of E-FABP deficiency or excess or deficiency of RA. In ontogeny, the septoclasts are differentiated from the pericytes and involved in the resorption of the uncalcified matrix of the cartilage templates in endochondral ossification. CONCLUSION: Septoclasts originate from pericytes and express E-FABP to play crucial roles in uncalcified matrix resorption by LCFA metabolism and RA signaling during endochondral ossification.
Usefulness of Thiel-Embalmed Cadavers for Training in Organ Procurement. International-journal

Hiroaki Mitsugashira, Kazuaki Tokodai, Wataru Nakanishi, Atsushi Fujio, Toshiaki Kashiwadate, Koji Miyazawa, Kengo Sasaki, Shigehito Miyagi, Yuji Owada, Michiaki Unno, Takashi Kamei

Transplantation proceedings　54　(2)　230-232　2022/03

DOI： 10.1016/j.transproceed.2021.10.026 　

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BACKGROUND: The number of brain-dead donors has been increasing; however, the opportunity for young surgeons to experience deceased donor surgeries is extremely limited, especially in many Asian countries including Japan. Deceased donor surgeries require unique surgical skills and knowledge; however, it is difficult to provide on-the-job guidance and education. Therefore, cadaver training is meaningful and suitable for the training of deceased donor surgeries. Thiel's embalming method (TEM) provides natural coloration, flexibility, and tissue plasticity, and is widely used for cadaver surgical training. In this study, we evaluated the usefulness of Thiel's embalmed cadaver training for organ procurement surgery. MATERIAL AND METHODS: Each trainee performed hepatectomy, pancreatectomy, and nephrectomy using conventional open techniques. Faculty experts of transplantation surgery and organ procurement took attendees through surgical steps. After the procedure, all participants were asked to complete a voluntary, anonymous survey, consisting of a 10-point satisfaction scale, to evaluate their perceptions of the training. RESULTS: A total of 33 gastrointestinal surgeons participated in the training program for procuring the liver, pancreas, and kidneys. In the questionnaire administered to the participants, the evaluation was generally satisfactory, with an average of 9.1 points on the 10-point scales. Some participants expressed that Thiel-embalmed cadavers are more suitable for training on organ procurement compared with animals used in wet-lab training. CONCLUSION: We conclude that organ procurement training in human cadavers preserved by TEM is useful and suitable for practicing deceased donor organ procurement, especially in countries where deceased donors are not common, as in Japan.
SGLT-1-specific inhibition ameliorates renal failure and alters the gut microbial community in mice with adenine-induced renal failure. International-journal

Hsin-Jung Ho, Koichi Kikuchi, Daiki Oikawa, Shun Watanabe, Yoshitomi Kanemitsu, Daisuke Saigusa, Ryota Kujirai, Wakako Ikeda-Ohtsubo, Mariko Ichijo, Yukako Akiyama, Yuichi Aoki, Eikan Mishima, Yoshiaki Ogata, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Takafumi Toyohara, Chitose Suzuki, Takehiro Suzuki, Nariyasu Mano, Yoshiteru Kagawa, Yuji Owada, Takane Katayama, Toru Nakayama, Yoshihisa Tomioka, Takaaki Abe

Physiological reports　9　(24)　e15092　2021/12

DOI： 10.14814/phy2.15092 　

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Sodium-dependent glucose cotransporters (SGLTs) have attracted considerable attention as new targets for type 2 diabetes mellitus. In the kidney, SGLT2 is the major glucose uptake transporter in the proximal tubules, and inhibition of SGLT2 in the proximal tubules shows renoprotective effects. On the other hand, SGLT1 plays a role in glucose absorption from the gastrointestinal tract, and the relationship between SGLT1 inhibition in the gut and renal function remains unclear. Here, we examined the effect of SGL5213, a novel and potent intestinal SGLT1 inhibitor, in a renal failure (RF) model. SGL5213 improved renal function and reduced gut-derived uremic toxins (phenyl sulfate and trimethylamine-N-oxide) in an adenine-induced RF model. Histological analysis revealed that SGL5213 ameliorated renal fibrosis and inflammation. SGL5213 also reduced gut inflammation and fibrosis in the ileum, which is a primary target of SGL5213. Examination of the gut microbiota community revealed that the Firmicutes/Bacteroidetes ratio, which suggests gut dysbiosis, was increased in RF and SGL5213 rebalanced the ratio by increasing Bacteroidetes and reducing Firmicutes. At the genus level, Allobaculum (a major component of Erysipelotrichaceae) was significantly increased in the RF group, and this increase was canceled by SGL5213. We also measured the effect of SGL5213 on bacterial phenol-producing enzymes that catalyze tyrosine into phenol, following the reduction of phenyl sulfate, which is a novel marker and a therapeutic target for diabetic kidney disease DKD. We found that the enzyme inhibition was less potent, suggesting that the change in the microbial community and the reduction of uremic toxins may be related to the renoprotective effect of SGL5213. Because SGL5213 is a low-absorbable SGLT1 inhibitor, these data suggest that the gastrointestinal inhibition of SGLT1 is also a target for chronic kidney diseases.
Nuclear FABP7 regulates cell proliferation of wild-type IDH1 glioma through caveolae formation. International-journal

Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Masayuki Kanamori, Ryo Zama, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Tunyanat Wannakul, Shuhan Yang, Teiji Tominaga, Yuji Owada

Molecular oncology　16　(1)　289-306　2021/10/30

DOI： 10.1002/1878-0261.13130 　

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Isocitrate dehydrogenase 1 (IDH1) is a key enzyme in cellular metabolism. IDH1 mutation (IDH1mut) is the most important genetic alteration in lower grade glioma, whereas glioblastoma (GB), the most common malignant brain tumor, often has wild-type IDH1 (IDH1wt). Although there is no effective treatment yet for neither IDH1wt nor IDHmut GB, it is important to note that the survival span of IDH1wt GB patients is significantly shorter than those with IDH1mut GB. Thus, understanding IDH1wt GB biology and developing effective molecular-targeted therapies is of paramount importance. Fatty acid-binding protein 7 (FABP7) is highly expressed in GB, and its expression level is negatively correlated with survival in malignant glioma patients; however, the underlying mechanisms of FABP7 involvement in tumor proliferation are still unknown. In this study, we demonstrate that FABP7 is highly expressed and localized in nuclei in IDH1wt glioma. Wild-type FABP7 (FABP7wt) overexpression in IDH1wt U87 cells increased cell proliferation rate, caveolin-1 expression, and caveolae/caveosome formation. In addition, FABP7wt overexpression increased the levels of H3K27ac on the caveolin-1 promoter through controlling the nuclear acetyl-CoA level via the interaction with ACLY. Consistent results were obtained using a xenograft model transplanted with U87 cells overexpressing FABP7. Interestingly, in U87 cells with mutant FABP7 overexpression, both in vitro and in vivo phenotypes shown by FABP7wt overexpression were disrupted. Furthermore, IDH1wt patient GB showed upregulated caveolin-1 expression, increased levels of histone acetylation, and increased levels of acetyl-CoA compared with IDH1mut patient GB. Taken together, these data suggest that nuclear FABP7 is involved in cell proliferation of GB through caveolae function/formation regulated via epigenetic regulation of caveolin-1, and this mechanism is critically important for IDH1wt tumor biology.
Curcumin Analog GO-Y030 Boosts the Efficacy of Anti-PD-1 Cancer Immunotherapy. International-journal

Takashi MaruYama, Shuhei Kobayashi, Hiroyuki Shibata, WanJun Chen, Yuji Owada

Cancer science　112　(12)　4844-4852　2021/09/16

DOI： 10.1111/cas.15136 　

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Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity Programmed cell death protein 1 (PD-1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti-PD-1 antibody, is known to promote the proliferation of the Treg population in tumor-infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO-Y030, an anti-tumor chemical. GO-Y030 inhibited the immune-suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO-Y030 inhibited the mTOR-S6 axis in Tregs, which plays a pivotal role in their immune-suppressive ability. GO-Y030 also controlled the metabolism in cultured CD4+ T cells in the presence of TGF-β + IL-6; however, it did not prevent Th17 differentiation. Notably, GO-Y030 significantly inhibited IL-10 production from Th17 cells. In the tumor microenvironment, L-lactate produced by tumors is known to support the suppressive ability of Tregs and GO-Y030-treatment inhibited L-lactate production via metabolic changes. In addition, experiments in the B16-F10 melanoma mouse model revealed that GO-Y030 helped inhibit the anti-PD-1 immune checkpoint and reduce the Treg population in tumor-infiltrating lymphocytes. Thus, GO-Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti-immune checkpoint inhibitors.
Fatty acid-binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment. International-journal

Shuhei Kobayashi, Tunyanat Wannakul, Kaname Sekino, Yu Takahashi, Yoshiteru Kagawa, Hirofumi Miyazaki, Banlanjo Abdulaziz Umaru, Shuhan Yang, Yui Yamamoto, Yuji Owada

International journal of cancer　150　(1)　152-163　2021/08/27

DOI： 10.1002/ijc.33777 　

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Plasmacytoid dendritic cells (pDCs) promote viral elimination by producing large amounts of Type I interferon. Recent studies have shown that pDCs regulate the pathogenesis of diverse inflammatory diseases, such as cancer. Fatty acid-binding protein 5 (FABP5) is a cellular chaperone of long-chain fatty acids that induce biological responses. Although the effects of FABP-mediated lipid metabolism are well studied in various immune cells, its role in pDCs remains unclear. This study, which compares wild-type and Fabp5-/- mice, provides the first evidence that FABP5-mediated lipid metabolism regulates the commitment of pDCs to inflammatory vs tolerogenic gene expression patterns in the tumor microenvironment and in response to toll-like receptor stimulation. Additionally, we demonstrated that FABP5 deficiency in pDCs affects the surrounding cellular environment, and that FABP5 expression in pDCs supports the appropriate generation of regulatory T cells (Tregs). Collectively, our findings reveal that pDC FABP5 acts as an important regulator of tumor immunity by controlling lipid metabolism.
Possible involvement of fatty acid binding proteins in psychiatric disorders.

Yui Yamamoto, Yuji Owada

Anatomical science international　96　(3)　333-342　2021/06

DOI： 10.1007/s12565-020-00598-0 　

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Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. Increasing evidence has shown that an imbalance of PUFAs is associated with various human psychiatric disorders, including autism and schizophrenia. However, the mechanisms underlying the effects of PUFAs on brain functions at cellular and molecular levels remain unclear. Since PUFAs are insoluble in water, specific transporters are required to deliver PUFAs to appropriate intracellular compartments. Fatty acid-binding proteins (FABPs), the cellular chaperones of PUFAs, are involved in PUFA intracellular trafficking, signal transduction, and gene transcription. Therefore, we focused on the relationship between FABP-regulated PUFA homeostasis in the brain and neuronal plasticity. The authors previously reported that FABP3, which preferentially binds to n-6 PUFAs, is strongly expressed in the gamma-aminobutyric acid (GABAergic) inhibitory interneurons of the adult mouse anterior cingulate cortex (ACC), which is a component of the limbic cortex and is important for the coordination of cognitive and emotional behaviors. Interestingly, Fabp3 KO mice show increased GABA synthesis and abnormal excitatory/inhibitory balance in the ACC. In addition, studies have indicated that FABP7, which preferentially binds to n-3 PUFAs, controls lipid raft function in astrocytes, and astrocytic Fabp7 deficiency results in an altered response of astrocytes to external stimuli. Furthermore, Fabp7 KO mice exhibit aberrant dendritic morphology, and decreased spine density and excitatory synaptic transmission in pyramidal neurons. This review summarizes relationship between PUFAs or FABPs and human psychiatric disorders and discusses recent progress in elucidating the function of FABPs, especially FABP3 and 7, in the brain.
Suppression of α-synuclein propagation after intrastriatal injection in FABP3 null mice. International-journal

Kazuya Matsuo, Ichiro Kawahata, Ronald Melki, Luc Bousset, Yuji Owada, Kohji Fukunaga

Brain research　1760　147383-147383　2021/06/01

DOI： 10.1016/j.brainres.2021.147383 　

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Accumulation and aggregation of α-synuclein (αSyn) trigger neuronal loss in the substantia nigra pars compacta (SNpc), which in turn causes motor symptoms in Parkinson's disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3), an intracellular fatty acid carrier protein, enhances αSyn neurotoxicity in SNpc and motor impairments after intranigral injection of αSyn fibrils. However, the temporal profile of αSyn fibril spread and their toxicity remains unclear. In the present study, we investigated the temporal profile of αSyn fibril spread and its toxicity, which induces intracellular fibril formation. Monomeric and fibrillar aSyn assemblies were labeled with ATTO550 to distinguish the exogenous form from the endogenous species and injected into bilateral striatum in Fabp3+/+ (wild type) and Fabp3-/- mice. Accumulation of both monomeric and fibrillar exogenous αSyn in the SNpc was drastically decreased in Fabp3-/- mice compared to that in the Fabp3+/+ counterparts. Deletion of Fabp3 also prevented exogenous αSyn fibril-induced seeding of the endogenous αSyn into aggregates containing phosphorylated and filamentous forms in the SNpc. Consistent with these results, loss of dopaminergic neurons and subsequent impaired motor behavior were attenuated in Fabp3-/- mice. These results highlight the crucial role of FABP3 in pathogenic αSyn accumulation and its seeding ability. Taken together, FABP3 could be a potential therapeutic target against αSyn propagation in synucleinopathies.
Ndufs4 ablation decreases synaptophysin expression in hippocampus. International-journal

Subrata Kumar Shil, Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Fumika Nanto-Hara, Hirofumi Miyazaki, Yui Yamamoto, Shuhei Kobayashi, Chitose Suzuki, Takaaki Abe, Yuji Owada

Scientific reports　11　(1)　10969-10969　2021/05/26

DOI： 10.1038/s41598-021-90127-4 　

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Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.
Fatty acid-binding protein 5 controls lung tumor metastasis by regulating the maturation of natural killer cells in the lung. International-journal

Shuhan Yang, Shuhei Kobayashi, Kaname Sekino, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Banlanjo Abdulaziz Umaru, Tunyanat Wannakul, Yuji Owada

FEBS letters　595　(13)　1797-1805　2021/05/12

DOI： 10.1002/1873-3468.14106 　

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Fatty acid-binding protein (FABP) 5 is highly expressed in various types of tumors and is strongly correlated with tumor growth, development, and metastasis. However, it is unclear how the expression of FABP5 in the host affects tumor progression. In this study, using a lung tumor metastasis model in mice, we found that FABP5-deficient mice were more susceptible to tumor metastasis, which is accompanied by infiltration of a lower frequency of activated natural killer (NK) cells in the lung. Additionally, FABP5 deficiency leads to impaired maturation of NK cells in the lungs, but not in the bone marrow and spleen. Taken together, our results provide the first evidence that FABP5 in the host regulates lung tumor metastasis through controlling NK cell maturation.
Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons. International-journal

Tomonori Hara, Manabu Toyoshima, Yasuko Hisano, Shabeesh Balan, Yoshimi Iwayama, Harumi Aono, Yushi Futamura, Hiroyuki Osada, Yuji Owada, Takeo Yoshikawa

Translational psychiatry　11　(1)　275-275　2021/05/08

DOI： 10.1038/s41398-021-01392-w 　

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Carbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, we found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger. Our observations can be used for designing an intervention strategy for diseases, particularly those induced by enhanced carbonyl stress or oxidative stress.
Functional Analysis of the Transcriptional Regulator IκB-ζ in Intestinal Homeostasis. International-journal

Tomoki Sasaki, Hiroyuki Nagashima, Atsushi Okuma, Takeshi Yamauchi, Kenshi Yamasaki, Setsuya Aiba, Takanori So, Naoto Ishii, Yuji Owada, Takashi MaruYama, Shuhei Kobayashi

Digestive diseases and sciences　67　(4)　1252-1259　2021/04/05

DOI： 10.1007/s10620-021-06958-8 　

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BACKGROUND: The Toll-like receptor signaling pathway contributes to the regulation of intestinal homeostasis through interactions with commensal bacteria. Although the transcriptional regulator IκB-ζ can be induced by Toll-like receptor signaling, its role in intestinal homeostasis is still unclear. AIMS: To investigate the role of IκB-ζ in gut homeostasis. METHODS: DSS-administration induced colitis in control and IκB-ζ-deficient mice. The level of immunoglobulins in feces was detected by ELISA. The immunological population in lamina propria (LP) was analyzed by FACS. RESULTS: IκB-ζ-deficient mice showed severe inflammatory diseases with DSS administration in the gut. The level of IgM in the feces after DSS administration was less in IκB-ζ-deficient mice compared to control mice. Upon administration of DSS, IκB-ζ-deficient mice showed exaggerated intestinal inflammation (more IFN-g-producing CD4+ T cells in LP), and antibiotic treatment canceled this inflammatory phenotype. CONCLUSION: IκB-ζ plays a crucial role in maintaining homeostasis in the gut.
Expression and enhancement of FABP4 in septoclasts of the growth plate in FABP5-deficient mouse tibiae. International-journal

Yasuhiko Bando, Nobuko Tokuda, Yudai Ogasawara, Go Onozawa, Arata Nagasaka, Koji Sakiyama, Yuji Owada, Osamu Amano

Histochemistry and cell biology　155　(4)　439-449　2021/04

DOI： 10.1007/s00418-020-01953-y 　

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In our previous study, fatty acid-binding protein 5 (FABP5) was expressed in septoclasts with long processes which are considered to resorb uncalcified matrix of the growth plate (GP) cartilage, and no apparent abnormalities were detected in the histo-architecture of the GP of FABP5-deficient (FABP5-/-) mice. Those finding lead us to hypothesize that another FABP can compensate the deletion of FABP5 in septoclasts of its gene-mutant mice. Based on the hypothesis, the present study examined the expression levels of several other FABPs in septoclasts and their morphology in FABP5-/- mouse tibiae. Processes of FABP5-/- septoclasts tend to be shorter than wild septoclasts. FABP4-positive septoclasts in FABP5-/- mice were more numerous than those cells in wild mice.Peroxisome proliferator-activated receptor (PPAR) γ was expressed in FABP4-positive septoclasts of FABP5-/- mice as well as mice administered with GW1929, a PPARγ agonist, suggesting that the occurrence of PPARγ induces an increase of FABP4-positive septoclasts. The present finding suggests that the functional exertion of FABP5 in septoclasts is supplemented by FABP4 in normal and FABP5-/- mice, and that the expression of FABP4 is up-regulated in accompany with PPARγ in FABP5-/- for maintenance of resorptive activity in the GP.
Ligand Bound Fatty Acid Binding Protein 7 (FABP7) Drives Melanoma Cell Proliferation Via Modulation of Wnt/β-Catenin Signaling. International-journal

Banlanjo Abdulaziz Umaru, Yoshiteru Kagawa, Subrata Kumar Shil, Naoki Arakawa, Yijun Pan, Hirofumi Miyazaki, Shuhei Kobayashi, Shuhan Yang, An Cheng, Yifei Wang, Yasuharu Shinoda, Yukiko Kiniwa, Ryuhei Okuyama, Kohji Fukunaga, Yuji Owada

Pharmaceutical research　38　(3)　479-490　2021/03

DOI： 10.1007/s11095-021-03009-9 　

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PURPOSE: Fatty acid-binding protein 7 (FABP7) involved in intracellular lipid dynamics, is highly expressed in melanomas and associated with decreased patient survival. Several studies put FABP7 at the center of melanoma cell proliferation. However, the underlying mechanisms are not well deciphered. This study examines the effects of FABP7 on Wnt/β-catenin signaling that enhances proliferation in melanoma cells. METHODS: Skmel23 cells with FABP7 silencing and Mel2 cells overexpressed with wild-type FABP7 (FABP7wt) and mutated FABP7 (FABP7mut) were used. Cell proliferation and migration were analyzed by proliferation and wound-healing assay, respectively. Transcriptional activation of the Wnt/β-catenin signaling was measured by luciferase reporter assay. The effects of a specific FABP7 inhibitor, MF6, on proliferation, migration, and modulation of the Wnt/β-catenin signaling were examined. RESULTS: FABP7 siRNA knockdown in Skmel23 decreased proliferation and migration, cyclin D1 expression, as well as Wnt/β-catenin activity. Similarly, FABP7wt overexpression in Mel2 cells increased these effects, but FABP7mut abrogated these effects. Pharmacological inhibition of FABP7 function with MF6 suppressed FABP7-regulated proliferation of melanoma cells. CONCLUSION: These results suggest the importance of the interaction between FABP7 and its ligands in melanoma proliferation modulation, and the beneficial implications of therapeutic targeting of FABP7 for melanoma treatment.
The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells. International-journal

Takashi MaruYama, Shuhei Kobayashi, Hiroko Nakatsukasa, Yuki Moritoki, Daiki Taguchi, Yoichi Sunagawa, Tatsuya Morimoto, Atsuko Asao, Wenwen Jin, Yuji Owada, Naoto Ishii, Yoshiharu Iwabuchi, Akihiko Yoshimura, WanJun Chen, Hiroyuki Shibata

Frontiers in immunology　12　687669-687669　2021

DOI： 10.3389/fimmu.2021.687669 　

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Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3+ Tregs from naïve CD4+ T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3+ Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability.
Crucial Role of FABP3 in αSyn-Induced Reduction of Septal GABAergic Neurons and Cognitive Decline in Mice. International-journal

Kazuya Matsuo, Yasushi Yabuki, Ronald Melki, Luc Bousset, Yuji Owada, Kohji Fukunaga

International journal of molecular sciences　22　(1)　2021/01/01

DOI： 10.3390/ijms22010400 　

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In synucleinopathies, while motor symptoms are thought to be attributed to the accumulation of misfolded α-synuclein (αSyn) in nigral dopaminergic neurons, it remains to be elucidated how cognitive decline arises. Here, we investigated the effects of distinct αSyn strains on cognition and the related neuropathology in the medial septum/diagonal band (MS/DB), a key region for cognitive processing. Bilateral injection of αSyn fibrils into the dorsal striatum potently impaired cognition in mice. The cognitive decline was accompanied by accumulation of phosphorylated αSyn at Ser129 and reduction of gamma-aminobutyric acid (GABA)-ergic but not cholinergic neurons in the MS/DB. Since we have demonstrated that fatty acid-binding protein 3 (FABP3) is critical for αSyn neurotoxicity in nigral dopaminergic neurons, we investigated whether FABP3 also participates in αSyn pathology in the MS/DB and cognitive decline. FABP3 was highly expressed in GABAergic but rarely in cholinergic neurons in the MS/DB. Notably, Fabp3 deletion antagonized the accumulation of phosphorylated αSyn, decrease in GABAergic neurons, and cognitive impairment caused by αSyn fibrils. Overall, the present study indicates that FABP3 mediates αSyn neurotoxicity in septal GABAergic neurons and the resultant cognitive impairment, and that FABP3 in this subpopulation could be a therapeutic target for dementia in synucleinopathies.
Fatty acid-binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4+ γ/δ T cell in a murine model. International-journal

Shuhei Kobayashi, Hai The Phung, Yoshiteru Kagawa, Hirofumi Miyazaki, Yu Takahashi, Atsuko Asao, Takashi Maruyama, Akihiko Yoshimura, Naoto Ishii, Yuji Owada

Allergy　76　(6)　1776-1788　2020/10/22

DOI： 10.1111/all.14630 　

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BACKGROUND: Fatty acid-binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear. METHODS: Contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild-type and Fabp3-/- mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co-culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3. RESULTS: Fabp3-deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL-17-producing Vγ4+ γ/δ T cells that critically control skin inflammation. In Fabp3-/- mice, we found a larger proportion of Vγ4+ γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3-/- mice also contained a higher amount of Vγ4+ γ/δ T cells not only in the skin but in the thymus when compared with wild-type mice. Furthermore, thymic double-negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4+ γ/δ T cells in the thymus. CONCLUSIONS: These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4+ γ/δ T-cell generation in the thymus.
Fatty acid-binding protein 5 limits ILC2-mediated allergic lung inflammation in a murine asthma model. International-journal

Shuhei Kobayashi, Shunichi Tayama, Hai The Phung, Yoshiteru Kagawa, Hirofumi Miyazaki, Yu Takahashi, Takashi Maruyama, Naoto Ishii, Yuji Owada

Scientific reports　10　(1)　16617-16617　2020/10/06

DOI： 10.1038/s41598-020-73935-y 　

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Dietary obesity is regarded as a problem worldwide, and it has been revealed the strong linkage between obesity and allergic inflammation. Fatty acid-binding protein 5 (FABP5) is expressed in lung cells, such as alveolar epithelial cells (ECs) and alveolar macrophages, and plays an important role in infectious lung inflammation. However, we do not know precise mechanisms on how lipid metabolic change in the lung affects allergic lung inflammation. In this study, we showed that Fabp5-/- mice exhibited a severe symptom of allergic lung inflammation. We sought to examine the role of FABP5 in the allergic lung inflammation and demonstrated that the expression of FABP5 acts as a novel positive regulator of ST2 expression in alveolar ECs to generate retinoic acid (RA) and supports the synthesis of RA from type II alveolar ECs to suppress excessive activation of innate lymphoid cell (ILC) 2 during allergic lung inflammation. Furthermore, high-fat diet (HFD)-fed mice exhibit the downregulation of FABP5 and ST2 expression in the lung tissue compared with normal diet (ND)-fed mice. These phenomena might be the reason why obese people are more susceptible to allergic lung inflammation. Thus, FABP5 is potentially a therapeutic target for treating ILC2-mediated allergic lung inflammation.
Mitochondrial dysfunction in GnRH neurons impaired GnRH production. International-journal

Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Subrata Kumar Shil, Ken Hayasaka, Ryo Zama, Yuta Kobayashi, Hirofumi Miyazaki, Shuhei Kobayashi, Chitose Suzuki, Yukio Katori, Takaaki Abe, Yuji Owada

Biochemical and biophysical research communications　530　(1)　329-335　2020/09/10

DOI： 10.1016/j.bbrc.2020.07.090 　

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The onset establishment and maintenance of gonadotropin-releasing hormone (GnRH) secretion is an important phenomenon regulating pubertal development and reproduction. GnRH neurons as well as other neurons in the hypothalamus have high-energy demands and require a constant energy supply from their mitochondria machinery to maintain active functioning. However, the involvement of mitochondrial function in GnRH neurons is still unclear. In this study, we examined the role of NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4), a member of the mitochondrial complex 1, on GnRH neurons using Ndufs4-KO mice and Ndufs4-KO GT1-7 cells. Ndufs4 was highly expressed in GnRH neurons in the medial preoptic area (MPOA) and NPY/AgRP and POMC neurons in the arcuate (ARC) nucleus in WT mice. Conversely, there was a significant decrease in GnRH expression in MPOA and median eminence of Ndufs4-KO mice, followed by impaired peripheral endocrine system. In Ndufs4-KO GT1-7 cells, Gnrh1 expression was significantly decreased with or without stimulation with either kisspeptin or NGF, whereas, stimulation significantly increased Gnrh1 expression in control cells. In contrast, there was no difference in cell signaling activity including ERK and CREB as well as the expression of GPR54, TrkA and p75NTR, suggesting that Ndufs4 is involved in the transcriptional regulation system for GnRH production. These findings may be useful in understanding the mitochondrial function in GnRH neuron.
Fatty Acid Binding Protein 7 is Involved in the Proliferation of Reactive Astrocytes, but not in Cell Migration and Polarity.

Tomonori Hara, Banlanjo Abdulaziz Umaru, Kazem Sharifi, Takeo Yoshikawa, Yuji Owada, Yoshiteru Kagawa

Acta histochemica et cytochemica　53　(4)　73-81　2020/08/26

DOI： 10.1267/ahc.20001 　

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Reactive gliosis is a defense mechanism to minimize and repair the initial damage after CNS injuries that is characterized by increases in astrocytic reactivity and proliferation, with enhanced expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Fatty acid binding protein 7 (FABP7) is abundantly expressed in several types of glial cells, such as astrocytes and oligodendrocyte precursor cells, during brain development and FABP7-positive astrocytes have been shown to be significantly increased in the mouse cortex after a stab injury. However, the functional significance of FABP7 in gliosis remains unclear. In the present study, we examined the mechanism of FABP7-mediated regulation of gliosis using an in vitro scratch-injury model using primary cultured astrocytes. Western blotting showed that FABP7 expression was increased significantly in scratch wounded astrocytes at the edge of the injury compared with intact astrocytes. Through monitoring the occupancy of the injured area, FAB7-KO astrocytes showed a slower proliferation rate compared with WT astrocytes after 48 hr, which was confirmed by BrdU immunostaining. There were no differences in cell migration and polarity of reactive astrocytes between FABP-KO and WT. Conclusively, our data suggest that FABP7 is important in the proliferation of reactive astrocytes in the context of CNS injury.
FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes. International-journal Peer-reviewed

Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Hiroki Shima, Ryo Ito, Ryo Zama, Ariful Islam, Shin-Ichiro Kanno, Akira Yasui, Shun Sato, Kosuke Jozaki, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Yui Yamamoto, Hiroshi Kogo, Chie Shimamoto-Mitsuyama, Akira Sugawara, Norihiro Sugino, Masayuki Kanamori, Teiji Tominaga, Takeo Yoshikawa, Kohji Fukunaga, Kazuhiko Igarashi, Yuji Owada

Molecular neurobiology　57　(12)　4891-4910　2020/08/19

DOI： 10.1007/s12035-020-02057-3 　

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Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.
Fatty acid‐binding protein 3 regulates differentiation of IgM‐producing plasma cells Peer-reviewed

Shuhei Kobayashi, Hai The Phung, Shunichi Tayama, Yoshiteru Kagawa, Hirofumi Miyazaki, Yui Yamamoto, Takashi Maruyama, Naoto Ishii, Yuji Owada

The FEBS Journal　288　(4)　1130-1141　2020/06/23
Publisher: Wiley
DOI： 10.1111/febs.15460 　

ISSN： 1742-464X

eISSN： 1742-4658
Fatty Acid Binding Protein 3 Enhances the Spreading and Toxicity of α-Synuclein in Mouse Brain Peer-reviewed

Yasushi Yabuki, Kazuya Matsuo, Ichiro Kawahata, Naoya Fukui, Tomohiro Mizobata, Yasushi Kawata, Yuji Owada, Norifumi Shioda, Kohji Fukunaga

International Journal of Molecular Sciences　2020/03/23

DOI： 10.3390/ijms21062230 　
Roles of fatty acid binding protein 7 in ischemic neuronal injury and ischemia-induced neurogenesis after transient forebrain ischemia. International-journal Peer-reviewed

Tatsuya Kato, Hideyuki Yoshioka, Yuji Owada, Hiroyuki Kinouchi

Brain research　1736　146795-146795　2020/03/14

DOI： 10.1016/j.brainres.2020.146795 　

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Fatty acid binding protein 7 (FABP7) has a protective role in the central nervous system injury and regulates neurogenesis during brain development; however, its roles in neuronal injury and neurogenesis after cerebral ischemia have not been elucidated. In this study, the expression of FABP7 after ischemia was studied and the effects of genetic FABP7 inhibition on neuronal injury and neurogenesis after ischemia were investigated. Male FABP7 knockout (KO) mice on a C57BL/6J background and their wild-type (WT) littermates were subjected to transient forebrain ischemia for 20 min. There was no difference in the level of neuronal injury between WT and KO mice. FABP7 expression was observed in neural stem/progenitor cells and increased 7-10 days after ischemia, which was consistent with the peak of hippocampal neurogenesis. In the KO mice, neurogenesis was significantly decreased compared with WT mice under both physiological and ischemic conditions. Differentiation from newborn cells to immature neurons was activated in the KO mice, but there was no difference in the number of cells that differentiated into mature neurons. These findings imply that FABP7 expressed in neuronal stem/progenitor cells regulates the proliferation and maintenance of newborn cells.
The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination. International-journal Peer-reviewed

Sarah Foerster, Alerie Guzman de la Fuente, Yoshiteru Kagawa, Theresa Bartels, Yuji Owada, Robin J M Franklin

Glia　2020/02/04

DOI： 10.1002/glia.23789 　

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The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one class of proteins known to bind FAs in a cell. Given the crucial role of FAs for myelin sheath formation we investigated the role of FABP7, the major isoform expressed in oligodendrocyte progenitor cells (OPCs), in developmental myelination and remyelination. Here, we show that the knockdown of Fabp7 resulted in a reduction of OPC differentiation in vitro. Consistent with this result, a delay in developmental myelination was observed in Fabp7 knockout animals. This delay was transient with full myelination being established before adulthood. FABP7 was dispensable for remyelination, as the knockout of Fapb7 did not alter remyelination efficiency in a focal demyelination model. In summary, while FABP7 is important in OPC differentiation in vitro, its function is not crucial for myelination and remyelination in vivo.
The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. International-journal Peer-reviewed

Fumika Nanto-Hara, Yoshitomi Kanemitsu, Shinji Fukuda, Koichi Kikuchi, Kei Asaji, Daisuke Saigusa, Tomoyuki Iwasaki, Hsin-Jung Ho, Eikan Mishima, Takehiro Suzuki, Chitose Suzuki, Tomoya Tsukimi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Yukako Akiyama, Shigeo Kure, Yuji Owada, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association　35　(2)　250-264　2020/02/01

DOI： 10.1093/ndt/gfz126 　

ISSN： 0931-0509

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BACKGROUND: Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. METHODS: Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. RESULTS: Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 μg/kg in the adenine-induced RF mouse model. At a high concentration of 100 μg/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-β, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the 'leaky gut' in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. CONCLUSION: Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut-cardio-renal axis.
TRAF5 promotes plasmacytoid dendritic cell development from bone marrow progenitors. International-journal Peer-reviewed

Shuhei Kobayashi, Yuka Shiota, Takeshi Kawabe, Hai The Phung, Takashi Maruyama, Yuji Owada, Takanori So, Naoto Ishii

Biochemical and biophysical research communications　521　(2)　353-359　2020/01/08

DOI： 10.1016/j.bbrc.2019.10.123 　

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The conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs) originate from the same common dendritic cell precursor cells in the bone marrow. The pDCs produce large amounts of type 1 interferon in response to foreign nucleic acid and crucially contribute to host defense against viral infection. Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a pivotal component of various TNF receptor signaling pathways in the immune system. Although the functions of TRAF5 in T and B lymphocytes have been well studied, its roles in pDCs remains to be fully elucidated. In this study, we show that the expression of TRAF5 supports the generation of pDCs in the bone marrow and also critically contributes to the homeostasis of the pDC subset in the periphery in a cell-intrinsic manner. Furthermore, we provide evidence that TRAF5 promotes the commitment of DC precursor cells toward pDC versus cDC subsets, which is regulated by the balance of transcription factors TCF4 and ID2. Together our findings reveal that TRAF5 acts as a positive regulator of pDC differentiation from bone marrow progenitors.
"Passenger gene" problem in transgenic C57BL/6 mice used in hearing research. International-journal Peer-reviewed

Jun Suzuki, Hitoshi Inada, Chul Han, Mi-Jung Kim, Ryuichi Kimura, Yusuke Takata, Yohei Honkura, Yuji Owada, Tetsuaki Kawase, Yukio Katori, Shinichi Someya, Noriko Osumi

Neuroscience research　158　6-15　2019/10/14

DOI： 10.1016/j.neures.2019.10.007 　

ISSN： 0168-0102

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Despite recent advances in genome engineering technologies, traditional transgenic mice generated on a mixed genetic background of C57BL/6 and 129/Sv mice remain widely used in age-related hearing loss (AHL) research, since C57BL/6 mice exhibit early onset and progression of AHL due to a mutation in cadherin 23-encoding gene (Cdh23753G>A). In these transgenic mice, backcrossing for more than 10 generations results in replacement of the donor background (129/Sv) with that of the recipient (C57BL/6), so that approximately 99.9% of genes are C57BL/6-derived and are considered congenic. However, the regions flanking the target gene may still be of 129/Sv origin, creating a so-called "passenger gene problem" where the normal 129/Sv-derived Cdh23753G allele can travel with the target gene. In this study, we investigated the role of fatty acid-binding protein 7 (Fabp7), which is important for cellular uptake and intracellular trafficking of fatty acids in the cochlea, using traditional Fabp7 knockout (KO) mice on the C57BL/6 background. We found that Fabp7 KO mice showed delayed AHL progression and milder cochlear degeneration. However, the genotype of the Cdh23 region flanking Fabp7 was still that of 129/Sv origin (Cdh23753GG). Our findings reveal the potential risk of contamination for traditional transgenic mice generated on the C57BL/6 background.
TNF Receptor-Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression. International-journal Peer-reviewed

Kobayashi S, Sakurai T, So T, Shiota Y, Asao A, Phung HT, Tanaka R, Kawabe T, Maruyama T, Kanno E, Kawakami K, Owada Y, Ishii N

Journal of immunology (Baltimore, Md. : 1950)　203　(6)　1447-1456　2019/09

DOI： 10.4049/jimmunol.1900188 　

ISSN： 0022-1767

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The physiological functions of TNF receptor-associated factor 5 (TRAF5) in the skin inflammation and wound healing process are not well characterized. We found that Traf5-/- mice exhibited an accelerated skin wound healing as compared with wild-type counterparts. The augmented wound closure in Traf5-/- mice was associated with a massive accumulation of plasmacytoid dendritic cells (pDCs) into skin wounds and an enhanced expression of genes related to wound repair at skin sites. In accordance with this result, adoptive transfer of Traf5-/- pDCs, but not wild-type pDCs, into the injured skin area in wild-type recipient mice significantly promoted skin wound healing. The expression of skin-tropic chemokine receptor CXCR3 was significantly upregulated in Traf5-/- pDCs, and treatment with a CXCR3 inhibitor cancelled the promoted wound healing in Traf5-/- mice, suggesting a pivotal role of CXCR3 in pDC-dependent wound healing. Traf5-/- pDCs displayed significantly higher expression of IFN regulatory factor 5 (IRF5), which correlated with greater induction of proinflammatory cytokine genes and CXCR3 protein after stimulation with TLR ligands. Consistently, transduction of exogeneous TRAF5 in Traf5-/- pDCs normalized the levels of abnormally elevated proinflammatory molecules, including IRF5 and CXCR3. Furthermore, knockdown of IRF5 also rescued the abnormal phenotypes of Traf5-/- pDCs. Therefore, the higher expression and induction of IRF5 in Traf5-/- pDCs causes proinflammatory and skin-tropic characteristics of the pDCs, which may accelerate skin wound healing responses. Collectively, our results uncover a novel role of TRAF5 in skin wound healing that is mediated by IRF5-dependent function of pDCs.
FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation. International-journal Peer-reviewed

Ariful Islam, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Banlanjo A Umaru, Yuki Yasumoto, Yui Yamamoto, Yuji Owada

Molecular neurobiology　56　(8)　5763-5779　2019/08

DOI： 10.1007/s12035-019-1489-2 　

ISSN： 0893-7648

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Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase 3 were observed in FABP7 KO astrocytes under ROS stress. N-acetyl L-cysteine (NAC) application successfully rescued the ROS toxicity in FABP7 KO astrocytes. Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher LD accumulation and higher antioxidant defence enzyme (TRX, TRX reductase 1 [TRXRD1]) expression than mock transfection and protected against apoptosis signalling (p38 MAPK, SAPK/JNK and cleaved caspase 3) activation. Taken together, these data suggest that FABP7 protects astrocytes from ROS toxicity through LD formation, providing new insights linking FABP7, lipid homeostasis, and neuropsychiatric/neurodegenerative disorders, including Alzheimer's disease and schizophrenia.
The role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis. International-journal Peer-reviewed

Kenyu Kamizato, Sho Sato, Subrata Kumar Shil, Banlanjo A Umaru, Yoshiteru Kagawa, Yui Yamamoto, Masaki Ogata, Yuki Yasumoto, Yuko Okuyama, Naoto Ishii, Yuji Owada, Hirofumi Miyazaki

Neuroscience　409　120-129　2019/06/15

DOI： 10.1016/j.neuroscience.2019.03.050 　

ISSN： 0306-4522

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Fatty acid binding protein 7 (FABP7) is expressed in astrocytes of the developing and mature central nervous system, and modulates astrocyte function by controlling intracellular fatty acid homeostasis. Astrocytes in the spinal cord have an important role in the process of myelin degeneration and regeneration. In the present study, the authors examined the role of FABP7 in astrocytes in a mouse model of experimental autoimmune encephalomyelitis (EAE), which is an established model of multiple sclerosis (MS). FABP7 was expressed in the white matter astrocytes and increased after EAE onset; particularly strong expression was observed in demyelinating regions. In FABP7-knockout (KO) mice, the onset of EAE symptoms occurred earlier than in wild type (WT) mice, and mRNA expression levels of inflammatory cytokines (IL-17 and TNF-α) were higher in FABP7-KO lumbar spinal cord than in WT lumbar spinal cord at early stage of EAE. Interestingly, however, the clinical score was significantly reduced in FABP7-KO mice compared with WT mice in the late phase of EAE. Moreover, the area exhibiting expression of fibronectin, which is an extracellular matrix protein mainly produced by astrocytes and inhibits remyelination of oligodendrocytes, was significantly decreased in FABP7-KO compared with WT mice. Collectively, FABP7 in astrocyte may have a role to protect from the induction of inflammation leading to demyelination in CNS at early phase of EAE. Moreover, FABP7 may be involved in the regulation of fibronectin production through the modification of astrocyte activation at late phase of EAE.
Effects of FABP7 on functional recovery after spinal cord injury in adult mice. Peer-reviewed

Senbokuya N, Yoshioka H, Yagi T, Owada Y, Kinouchi H

Journal of neurosurgery. Spine　1-7　2019/05

DOI： 10.3171/2019.2.SPINE18844 　

ISSN： 1547-5654
Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. International-journal Peer-reviewed

Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

Nature communications　10　(1)　1835-1835　2019/04/23

DOI： 10.1038/s41467-019-09735-4 　

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Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.
Evaluation of the role of fatty acid-binding protein 7 in controlling schizophrenia-relevant phenotypes using newly established knockout mice. International-journal Peer-reviewed

Shimamoto-Mitsuyama C, Ohnishi T, Balan S, Ohba H, Watanabe A, Maekawa M, Hisano Y, Iwayama Y, Owada Y, Yoshikawa T

Schizophrenia research　217　52-59　2019/02

DOI： 10.1016/j.schres.2019.02.002 　

ISSN： 0920-9964

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Dampened prepulse inhibition (PPI) is a consistent observation in psychiatric disorders, including schizophrenia and qualifies as a robust endophenotype for genetic evaluation. Using high PPI C57BL/6NCrlCrlj (B6Nj) and low PPI C3H/HeNCrlCrlj (C3HNj) inbred mouse strains, we have previously reported a quantitative trait locus (QTL) for PPI at chromosome 10 and identified Fabp7 as a candidate gene for regulating PPI and schizophrenia pathogenesis using Fabp7-deficient mice (B6.Cg-Fabp7 KO). Here, considering a possibility of carryover of residual genetic materials from embryonic stem (ES) cells used in generating knockout (KO) mice, we set out to re-address the genotype-phenotype correlation in a uniform genetic background. By generating a new Fabp7 KO mouse model in C57BL/6NCrl (B6N) background using the CRISPR-Cas9 nickase system, we evaluated the impact of Fabp7 ablation on schizophrenia-related behavioral phenotypes. To our surprise, we found no significant differences in PPI or any of the schizophrenia-related behavioral scores, as observed in our previous B6.Cg-Fabp7 KO mice. We identified several C3H/He mouse strain-specific alleles within the interval of chromosome 10-QTL, which are shared with 129/Sv mouse strains. These alleles, derived from 129/Sv ES cells, were retained in the B6.Cg-Fabp7 KO, despite multiple backcrossing and are thought to be responsible for the dampened PPI. In summary, our study demonstrates a precise genotype-phenotype relation for Fabp7 loss-of-function in a uniform B6N background, and raises the necessity of further analysis of the effects of genomic variants flanking the Fabp7 interval on phenotypes.
FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid Decarboxylase67 Promoter Region. International-journal Peer-reviewed

Yui Yamamoto, Hiroyuki Kida, Yoshiteru Kagawa, Yuki Yasumoto, Hirofumi Miyazaki, Ariful Islam, Masaki Ogata, Yuchio Yanagawa, Dai Mitsushima, Kohji Fukunaga, Yuji Owada

The Journal of neuroscience : the official journal of the Society for Neuroscience　38　(49)　10411-10423　2018/12/05

DOI： 10.1523/JNEUROSCI.1285-18.2018 　

ISSN： 0270-6474

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Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. Increasing evidence has shown that an imbalance of PUFAs is associated with various human psychiatric disorders, including autism and schizophrenia. Fatty acid-binding proteins (FABPs), cellular chaperones of PUFAs, are involved in PUFA intracellular trafficking, signal transduction, and gene transcription. In this study, we show that FABP3 is strongly expressed in the GABAergic inhibitory interneurons of the male mouse anterior cingulate cortex (ACC), which is a component of the limbic cortex and is important for the coordination of cognitive and emotional behaviors. Interestingly, Fabp3 KO male mice show an increase in the expression of the gene encoding the GABA-synthesizing enzyme glutamic acid decarboxylase 67 (Gad67) in the ACC. In the ACC of Fabp3 KO mice, Gad67 promoter methylation and the binding of methyl-CpG binding protein 2 (MeCP2) and histone deacetylase 1 (HDAC1) to the Gad67 promoter are significantly decreased compared with those in WT mice. The abnormal cognitive and emotional behaviors of Fabp3 KO mice are restored by methionine administration. Notably, methionine administration normalizes Gad67 promoter methylation and its mRNA expression in the ACC of Fabp3 KO mice. These findings demonstrate that FABP3 is involved in the control of DNA methylation of the Gad67 promoter and activation of GABAergic neurons in the ACC, thus suggesting the importance of PUFA homeostasis in the ACC for cognitive and emotional behaviors.SIGNIFICANCE STATEMENT The ACC is important for emotional and cognitive processing. However, the mechanisms underlying its involvement in the control of behavioral responses are largely unknown. We show the following new observations: (1) FABP3, a PUFA cellular chaperone, is exclusively expressed in GABAergic interneurons in the ACC; (2) an increase in Gad67 expression is detected in the ACC of Fabp3 KO mice; (3) the Gad67 promoter is hypomethylated and the binding of transcriptional repressor complexes is decreased in the ACC of Fabp3 KO mice; and (4) elevated Gad67 expression and abnormal behaviors seen in Fabp3 KO mice are mostly recovered by methionine treatment. These suggest that FABP3 regulates GABA synthesis through transcriptional regulation of Gad67 in the ACC.
Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus. International-journal Peer-reviewed

Yuki Yasumoto, Hirofumi Miyazaki, Masaki Ogata, Yoshiteru Kagawa, Yui Yamamoto, Ariful Islam, Tetsuya Yamada, Hideki Katagiri, Yuji Owada

Molecular neurobiology　55　(12)　9016-9028　2018/12

DOI： 10.1007/s12035-018-1033-9 　

ISSN： 0893-7648

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The hypothalamus is involved in the regulation of food intake and energy homeostasis. The arcuate nucleus (ARC) and median eminence (ME) are the primary hypothalamic sites that sense leptin and nutrients in the blood, thereby mediating food intake. Recently, studies demonstrating a role for non-neuronal cell types, including astrocytes and tanycytes, in these regulatory processes have begun to emerge. However, the molecular mechanisms involved in these activities remain largely unknown. In this study, we examined in detail the localization of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC and sought to determine its role in the hypothalamus. We performed a phenotypic analysis of diet-induced FABP7 knockout (KO) obese mice and of FABP7 KO mice treated with a single leptin injection. Immunohistochemistry revealed that FABP7+ cells are NG2+ or GFAP+ in the ARC and ME. In mice fed a high-fat diet, weight gain and food intake were lower in FABP7 KO mice than in wild-type (WT) mice. FABP7 KO mice also had lower food intake and weight gain after a single injection of leptin, and we consistently confirmed that the number of pSTAT3+ cells in the ARC indicated that the leptin-induced activation of neurons was significantly more frequent in FABP7 KO mice than in WT mice. In FABP7 KO mice-derived primary astrocyte cultures, the level of ERK phosphorylation was lower after leptin treatment. Collectively, these results indicate that in hypothalamic astrocytes, FABP7 might be involved in sensing neuronal leptin via glia-mediated mechanisms and plays a pivotal role in controlling systemic energy homeostasis.
Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma. International-journal Peer-reviewed

Nagao K, Shinohara N, Smit F, de Weijert M, Jannink S, Owada Y, Mulders P, Oosterwijk E, Matsuyama H

BMC cancer　18　(1)　1114-1114　2018/11

DOI： 10.1186/s12885-018-5060-8 　

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BACKGROUND: To identify potential therapeutic target in clear cell renal cell carcinoma (ccRCC), we performed a transcriptome analysis. Our analysis showed that fatty acid binding protein 7 (FABP7) has the highest mean differential overexpression in ccRCC compared to normal kidney. We aimed to investigate the significance of FABP7 in ccRCC. METHODS: Immunohistochemical staining for 40 advanced ccRCC cases was performed to investigate correlation between clinicopathological parameters and FABP7. They were composed of 40-83 years old cases with 33 male, 22 cases with pT ≥ 3, 19 cases with M1, and 16 cases with grade 3. The effect of gene knockdown was analysed by a cell viability assay and invasion assay in FABP7-overexpressing cell lines (SKRC7 and SKRC10). RESULTS: Our immunohistochemical analysis showed that higher FABP7 expression significantly correlated with distant metastasis and poor cancer-specific survival (CSS; both p < 0.05). Functional suppression of FABP7 significantly inhibited SKRC10 cell growth (p < 0.05) and resulted in a significant reduction of the invasive potential (p < 0.01), but did not cause growth inhibition of SKRC7 cells. We found that The Cancer Genome Atlas Research Network (TCGA) database shows FABP6 and 7 as equally overexpressed in the FABP family. Functional suppression of fatty acid binding protein 6 (FABP6) resulted in significant growth inhibition of SKRC7 cells (p < 0.005). CONCLUSIONS: Functional suppression of FABP7 significantly reduced cell viability and invasive potential in a ccRCC cell line. FABP7 may play a role in progression in some metastatic ccRCCs. The suppressed function may be compensated by another FABP family member.
Down-regulation of fatty acid binding protein 7 (Fabp7) is a hallmark of the postpartum brain. Peer-reviewed

Driessen TM, Zhao C, Saenz M, Stevenson SA, Owada Y, Gammie SC

Journal of chemical neuroanatomy　92　92-101　2018/10

DOI： 10.1016/j.jchemneu.2018.07.003 　

ISSN： 0891-0618
脂肪酸シグナリングに関与するFABP研究の新展開統合失調症と脂肪酸結合タンパク質

島本知英, 前川素子, 大西哲生, 豊田倫子, 岩山佳美, 大和田祐二, 吉川武男

日本生化学会大会プログラム・講演要旨集　91回　[1S10a-02]　2018/09
Publisher: (公社)日本生化学会
Role of FABP7 in tumor cell signaling. International-journal Peer-reviewed

Kagawa Y, Umaru BA, Ariful I, Shil SK, Miyazaki H, Yamamoto Y, Ogata M, Owada Y

Advances in biological regulation　71　206-218　2018/09

DOI： 10.1016/j.jbior.2018.09.006 　

ISSN： 2212-4926

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Lipids are major molecules for the function of organisms and are involved in the pathophysiology of various diseases. Fatty acids (FAs) signaling and their metabolism are some of the most important pathways in tumor development, as lipids serve as energetic sources during carcinogenesis. Fatty acid binding proteins (FABPs) facilitate FAs transport to different cell organelles, modulating their metabolism along with mediating other physiological activities. FABP7, brain-typed FABP, is thought to be an important molecule for cell proliferation in healthy as well as diseased organisms. Several studies on human tumors and tumor-derived cell lines put FABP7 in the center of tumorigenesis, and its high expression level has been reported to correlate with poor prognosis in different tumor types. Several types of FABP7-expressing tumors have shown an up-regulation of cell signaling activity, but molecular mechanisms of FABP7 involvement in tumorigenesis still remain elusive. In this review, we focus on the expression and function of FABP7 in different tumors, and possible mechanisms of FABP7 in tumor proliferation and migration.
Origin and development of septoclasts in endochondral ossification of mice Peer-reviewed

Yasuhiko Bando, Hide Sakashita, Fuyoko Taira, Genki Miyake, Yudai Ogasawara, Koji Sakiyama, Yuji Owada, Osamu Amano

Histochemistry and Cell Biology　149　(6)　645-654　2018/06/01
Publisher: Springer Verlag
DOI： 10.1007/s00418-018-1653-1 　

ISSN： 1432-119X 0948-6143
Ramelteon Improves Post-traumatic Stress Disorder-Like Behaviors Exhibited by Fatty Acid-Binding Protein 3 Null Mice. International-journal Peer-reviewed

Yasushi Yabuki, Ibuki Takahata, Kazuya Matsuo, Yuji Owada, Kohji Fukunaga

Molecular neurobiology　55　(4)　3577-3591　2018/04

DOI： 10.1007/s12035-017-0587-2 　

ISSN： 0893-7648

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We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 -/-) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2 receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably, chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3 -/- mice. Relevant to mechanisms underlying impaired fear extinction, we observed significantly reduced levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation without changes in ERK phosphorylation in the anterior cingulate cortex (ACC). Inversely, CaMKII autophosphorylation increased in the basolateral amygdala (BLA) but remained relatively unchanged in hippocampus of Fabp3 -/- mice. Likewise, the number of c-Fos-positive neurons in BLA significantly increased after exposure to contextual fear conditions but remained unchanged in the central nucleus of the amygdala (CeA). Importantly, chronic ramelteon administration (1.0 mg/kg, p.o.) restored abnormal c-Fos expression and CaMKII autophosphorylation in the ACC and BLA of Fabp3 -/- mice. Finally, the melatonin receptor antagonist luzindole (2.5 mg/kg, i.p.) blocked ramelteon-dependent improvements. Taken together, Fabp3 -/- mice show PTSD-like behaviors, and ramelteon is a likely attractive candidate for PTSD therapy.
Ultrastructural histometric evidence for expansion of the sustentacular cell envelope in response to hypersecretion of adrenal chromaffin cells in mice Peer-reviewed

Sawetree Pakkarato, Wipawee Thoungseabyoun, Apussara Tachow, Atsara Rawangwong, Yoshiteru Kagawa, Yuji Owada, Hisatake Kondo, Wiphawi Hipkaeo

Anatomical Science International　93　(1)　75-81　2018/01/01
Publisher: Springer Tokyo
DOI： 10.1007/s12565-016-0370-x 　

ISSN： 1447-073X 1447-6959
Dab1 contributes differently to the morphogenesis of the hippocampal subdivisions Peer-reviewed

Marissa Blume, Fuduki Inoguchi, Taku Sugiyama, Yuji Owada, Noriko Osumi, Yoshinari Aimi, Kosuke Taki, Yu Katsuyama

DEVELOPMENT GROWTH & DIFFERENTIATION　59　(8)　657-673　2017/10

DOI： 10.1111/dgd.12393 　

ISSN： 0012-1592

eISSN： 1440-169X
Epidural focal brain cooling abolishes neocortical seizures in cats and non-human primates Peer-reviewed

Takao Inoue, Masami Fujii, Hiroyuki Kida, Toshitaka Yamakawa, Yuichi Maruta, Tatsuji Tokiwa, Yeting He, Sadahiro Nomura, Yuji Owada, Takeshi Yamakawa, Michiyasu Suzuki

NEUROSCIENCE RESEARCH　122　35-44　2017/09

DOI： 10.1016/j.neures.2017.04.007 　

ISSN： 0168-0102

eISSN： 1872-8111
Retinoic acid regulates cell-shape and-death of E-FABP (FABP5)-immunoreactive septoclasts in the growth plate cartilage of mice Peer-reviewed

Yasuhiko Bando, Miyuki Yamamoto, Koji Sakiyama, Hide Sakashita, Fuyoko Taira, Genki Miyake, Shoichi Iseki, Yuji Owada, Osamu Amano

HISTOCHEMISTRY AND CELL BIOLOGY　148　(3)　229-238　2017/09

DOI： 10.1007/s00418-017-1578-0 　

ISSN： 0948-6143

eISSN： 1432-119X
Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders Peer-reviewed

Hideaki Imai, Hirotaka Shoji, Masaki Ogata, Yoshiteru Kagawa, Yuji Owada, Tsuyoshi Miyakawa, Kenji Sakimura, Toshio Terashima, Yu Katsuyama

CEREBRAL CORTEX　27　(7)　3485-3501　2017/07

DOI： 10.1093/cercor/bhv334 　

ISSN： 1047-3211

eISSN： 1460-2199
Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases Peer-reviewed

Tetsuro Matsuhashi, Takeya Sato, Shin-ichiro Kanno, Takehiro Suzuki, Akihiro Matsuo, Yuki Oba, Motoi Kikusato, Emi Ogasawara, Tai Kudo, Kosuke Suzuki, Osamu Ohara, Hiroko Shimbo, Fumika Nanto, Hiroaki Yamaguchi, Daisuke Saigusa, Yasuno Mukaiyama, Akiko Watabe, Koichi Kikuchi, Hisato Shima, Eikan Mishima, Yasutoshi Akiyama, Yoshitsugu Oikawa, Hsin-Jung Ho, Yukako Akiyama, Chitose Suzuki, Mitsugu Uematsu, Masaki Ogata, Naonori Kumagai, Masaaki Toyomizu, Atsushi Hozawa, Nariyasu Mano, Yuji Owada, Setsuya Aiba, Teruyuki Yanagisawa, Yoshihisa Tomioka, Shigeo Kure, Sadayoshi Ito, Kazuto Nakada, Ken-ichiro Hayashi, Hitoshi Osaka, Takaaki Abe

EBIOMEDICINE　20　27-38　2017/06

DOI： 10.1016/j.ebiom.2017.05.016 　

ISSN： 2352-3964
Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7 Peer-reviewed

Jason R. Gerstner, Isaac J. Perron, Samantha M. Riedy, Takeo Yoshikawa, Hiroshi Kadotani, Yuji Owada, Hans P. A. Van Dongen, Raymond J. Galante, Kaitlin Dickinson, Jerry C. P. Yin, Allan I. Pack, Marcos G. Frank

SCIENCE ADVANCES　3　(4)　e1602663　2017/04

DOI： 10.1126/sciadv.1602663 　

ISSN： 2375-2548
Microglia-derived neuregulin expression in psychiatric disorders. International-journal Peer-reviewed

Daisuke Ikawa, Manabu Makinodan, Keiko Iwata, Masahiro Ohgidani, Takahiro A Kato, Yasunori Yamashita, Kazuhiko Yamamuro, Sohei Kimoto, Michihiro Toritsuka, Takahira Yamauchi, Shin-Ichi Fukami, Hiroki Yoshino, Kazuki Okumura, Tatsuhide Tanaka, Akio Wanaka, Yuji Owada, Masatsugu Tsujii, Toshiro Sugiyama, Kenji Tsuchiya, Norio Mori, Ryota Hashimoto, Hideo Matsuzaki, Shigenobu Kanba, Toshifumi Kishimoto

Brain, behavior, and immunity　61　375-385　2017/03

DOI： 10.1016/j.bbi.2017.01.003 　

ISSN： 0889-1591

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Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.
Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge Peer-reviewed

Julia L. Gregory, Anne Walter, Yannick O. Alexandre, Jyh Liang Hor, Ruijie Liu, Joel Z. Ma, Sapna Devi, Nobuko Tokuda, Yuji Owada, Laura K. Mackay, Gordon K. Smyth, William R. Heath, Scott N. Mueller

CELL REPORTS　18　(2)　406-418　2017/01

DOI： 10.1016/j.celrep.2016.12.038 　

ISSN： 2211-1247
Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function Peer-reviewed

Yijun Pan, Jennifer L. Short, Kwok H. C. Choy, Annie X. Zeng, Philip J. Marriott, Yuji Owada, Martin J. Scanlon, Christopher J. H. Porter, Joseph A. Nicolazzo

JOURNAL OF NEUROSCIENCE　36　(46)　11755-11767　2016/11

DOI： 10.1523/JNEUROSCI.1583-16.2016 　

ISSN： 0270-6474
Results of Questionnaire Survey on Gross Anatomy Education (March 2014). Peer-reviewed

Yaginuma H, Matsumura G, Satoh YI, Iino S, Tsuruo Y, Owada Y, Fujiyama F, Amitzuka N

Kaibogaku zasshi. Journal of anatomy　91　(4)　33-40　2016/09

ISSN： 0022-7722
Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex Peer-reviewed

Hiroyuki Kida, Yasumasa Tsuda, Nana Ito, Yui Yamamoto, Yuji Owada, Yoshinori Kamiya, Dai Mitsushima

CEREBRAL CORTEX　26　(8)　3494-3507　2016/08

DOI： 10.1093/cercor/bhw134 　

ISSN： 1047-3211

eISSN： 1460-2199
Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina Peer-reviewed

Xinyi Su, Queenie S. W. Tan, Bhav H. Parikh, Alison Tan, Milan N. Mehta, Yeo Sia Wey, Sai Bo Bo Tun, Ling-Jun Li, Xiao-Yan Han, Tien Y. Wong, Walter Hunziker, Chi D. Luu, Yuji Owada, Veluchamy A. Barathi, Samuel S. Zhang, Shyam S. Chaurasia

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　57　(7)　3397-3408　2016/06

DOI： 10.1167/iovs.15-18542 　

ISSN： 0146-0404

eISSN： 1552-5783
Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4 Peer-reviewed

Koichi Fujisawa, Shuji Terai, Taro Takami, Naoki Yamamoto, Takahiro Yamasaki, Toshihiko Matsumoto, Kazuhito Yamaguchi, Yuji Owada, Hiroshi Nishina, Takafumi Noma, Isao Sakaida

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH　35　(No.1)　48-48　2016/03

DOI： 10.1186/s13046-016-0322-2 　

ISSN： 1756-9966
Omega-3 fatty acid transport through the placenta. Peer-reviewed

Islam A, Kodama T, Yamamoto Y, Ebrahimi M, Miyazaki H, Yasumoto Y, Kagawa Y, Sawada T, Owada Y, Tokuda N

Asian J. Med. Biol. Res.　2　(1)　1-8　2016/03
Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4. Peer-reviewed

Fujisawa K, Terai S, Takami T, Yamamoto N, Yamasaki T, Matsumoto T, Yamaguchi K, Owada Y, Nishina H, Noma T, Sakaida I

Journal of experimental & clinical cancer research : CR　35　48　2016/03

DOI： 10.1186/s13046-016-0322-2 　

ISSN： 0392-9078
Astrocyte-Expressed FABP7 Regulates Dendritic Morphology and Excitatory Synaptic Function of Cortical Neurons Peer-reviewed

Majid Ebrahimi, Yui Yamamoto, Kazem Sharifi, Hiroyuki Kida, Yoshiteru Kagawa, Yuki Yasumoto, Ariful Islam, Hirofumi Miyazaki, Chie Shimamoto, Motoko Maekawa, Dai Mitsushima, Takeo Yoshikawa, Yuji Owada

GLIA　64　(1)　48-62　2016/01

DOI： 10.1002/glia.22902 　

ISSN： 0894-1491

eISSN： 1098-1136
Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells Peer-reviewed

Yuki Yasumoto, Hirofumi Miyazaki, Linda Koshy Vaidyan, Yoshiteru Kagawa, Majid Ebrahimi, Yui Yamamoto, Masaki Ogata, Yu Katsuyama, Hirokazu Sadahiro, Michiyasu Suzuki, Yuji Owada

PLOS ONE　11　(1)　e0147717　2016/01

DOI： 10.1371/journal.pone.0147717 　

ISSN： 1932-6203
Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism (vol 5, 16239, 2015) Peer-reviewed

Motoko Maekawa, Yoshimi Iwayama, Tetsuo Ohnishi, Manabu Toyoshima, Chie Shimamoto, Yasuko Hisano, Tomoko Toyota, Shabeesh Balan, Hideo Matsuzaki, Yasuhide Iwata, Shu Takagai, Kohei Yamada, Motonori Ota, Satoshi Fukuchi, Yohei Okada, Wado Akamatsu, Masatsugu Tsujii, Nobuhiko Kojima, Yuji Owada, Hideyuki Okano, Norio Mori, Takeo Yoshikawa

SCIENTIFIC REPORTS　6　20268　2016/01

DOI： 10.1038/srep20268 　

ISSN： 2045-2322
精神疾患の病態生理と脂肪酸結合タンパク質の質的量的変化の関連性

島本知英, 大西哲生, 前川素子, 豊田倫子, 渡辺明子, 豊島学, 鈴木勝昭, 杉山栄二, 森則夫, 中村和彦, 瀬藤光利, 大和田祐二, 小林哲幸, 吉川武男

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[2P1265]-[2P1265]　2015/12
Publisher: (公社)日本生化学会
Fatty Acid-Binding Protein 5 Facilitates the Blood-Brain Barrier Transport of Docosahexaenoic Acid Peer-reviewed

Yijun Pan, Martin J. Scanlon, Yuji Owada, Yui Yamamoto, Christopher J. H. Porter, Joseph A. Nicolazzo

MOLECULAR PHARMACEUTICS　12　(12)　4375-4385　2015/12

DOI： 10.1021/acs.molpharmaceut.5b00580 　

ISSN： 1543-8384
Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism Peer-reviewed

Motoko Maekawa, Yoshimi Iwayama, Tetsuo Ohnishi, Manabu Toyoshima, Chie Shimamoto, Yasuko Hisano, Tomoko Toyota, Shabeesh Balan, Hideo Matsuzaki, Yasuhide Iwata, Shu Takagai, Kohei Yamada, Motonori Ota, Satoshi Fukuchi, Yohei Okada, Wado Akamatsu, Masatsugu Tsujii, Nobuhiko Kojima, Yuji Owada, Hideyuki Okano, Norio Mori, Takeo Yoshikawa

SCIENTIFIC REPORTS　5　16239　2015/11

DOI： 10.1038/srep16239 　

ISSN： 2045-2322
脂肪酸結合タンパク質の質的量的変化が精神疾患発症に寄与する可能性

島本知英, 大西哲生, 前川素子, 豊田倫子, 渡辺明子, 豊島学, 新井亮一, 鈴木勝昭, 中村和彦, 森則夫, 大和田祐二, 小林哲幸, 吉川武男

日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集　37回・45回　211-211　2015/09
Publisher: 日本生物学的精神医学会・日本神経精神薬理学会
精神疾患の病態生理に脂肪酸結合タンパク質が関与している可能性

島本知英, 大西哲生, 前川素子, 豊田倫子, 渡辺明子, 豊島学, 新井亮一, 鈴木勝昭, 中村和彦, 森則夫, 大和田祐二, 小林哲幸, 吉川武男

脂質栄養学　24　(2)　164-164　2015/08
Publisher: 日本脂質栄養学会
ISSN： 1343-4594

eISSN： 1883-2237
The Palm-Sized Cryoprobe System Based on Refrigerant Expansion and Boiling and Its Application to an Animal Model of Epilepsy Peer-reviewed

Tatsuji Tokiwa, Lev Zimin, Satoru Ishizuka, Takao Inoue, Masami Fujii, Hiroshi Ishiguro, Hiroshi Kajigaya, Yuji Owada, Michiyasu Suzuki, Takeshi Yamakawa

IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING　62　(8)　1949-1958　2015/08

DOI： 10.1109/TBME.2015.2407692 　

ISSN： 0018-9294

eISSN： 1558-2531
Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms Peer-reviewed

Martin Kaczocha, Sherrye T. Glaser, Thomas Maher, Brendan Clavin, John Hamilton, Joseph O'Rourke, Mario Rebecchi, Michelino Puopolo, Yuji Owada, Panayotis K. Thanos

MOLECULAR PAIN　11　52　2015/08

DOI： 10.1186/s12990-015-0056-8 　

ISSN： 1744-8069
Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses. International-journal Peer-reviewed

Motoko Maekawa, Kazuo Yamada, Manabu Toyoshima, Tetsuo Ohnishi, Yoshimi Iwayama, Chie Shimamoto, Tomoko Toyota, Yayoi Nozaki, Shabeesh Balan, Hideo Matsuzaki, Yasuhide Iwata, Katsuaki Suzuki, Mitsuhiro Miyashita, Mitsuru Kikuchi, Motoichiro Kato, Yohei Okada, Wado Akamatsu, Norio Mori, Yuji Owada, Masanari Itokawa, Hideyuki Okano, Takeo Yoshikawa

Biological psychiatry　78　(2)　116-25　2015/07/15

DOI： 10.1016/j.biopsych.2014.07.025 　

ISSN： 0006-3223

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BACKGROUND: Identifying beneficial surrogate genetic markers in psychiatric disorders is crucial but challenging. METHODS: Given that scalp hair follicles are easily accessible and, like the brain, are derived from the ectoderm, expressions of messenger RNA (mRNA) and microRNA in the organ were examined between schizophrenia (n for first/second = 52/42) and control subjects (n = 62/55) in two sets of cohort. Genes of significance were also analyzed using postmortem brains (n for case/control = 35/35 in Brodmann area 46, 20/20 in cornu ammonis 1) and induced pluripotent stem cells (n = 4/4) and pluripotent stem cell-derived neurospheres (n = 12/12) to see their role in the central nervous system. Expression levels of mRNA for autism (n for case/control = 18/24) were also examined using scalp hair follicles. RESULTS: Among mRNA examined, FABP4 was downregulated in schizophrenia subjects by two independent sample sets. Receiver operating characteristic curve analysis determined that the sensitivity and specificity were 71.8% and 66.7%, respectively. FABP4 was expressed from the stage of neurosphere. Additionally, microarray-based microRNA analysis showed a trend of increased expression of hsa-miR-4449 (p = .0634) in hair follicles from schizophrenia. hsa-miR-4449 expression was increased in Brodmann area 46 from schizophrenia (p = .0007). Finally, we tested the expression of nine putative autism candidate genes in hair follicles and found decreased CNTNAP2 expression in the autism cohort. CONCLUSIONS: Scalp hair follicles could be a beneficial genetic biomarker resource for brain diseases, and further studies of FABP4 are merited in schizophrenia pathogenesis.
Fatty Acid Binding Protein 5 (FABP5) Regulates Diet-induced Obesity (DIO) via GIP Secretion from Enteroendocrine K-cells in Response to Fat Ingestion Peer-reviewed

Shibue Kimitaka, Yamane Shunsuke, Harada Norio, Hamasaki Akihiro, Suzuki Kazuyo, Joo Erina, Iwasaki Kanako, Nasteska Daniela, Harada Takanari, Hayashi Yoshitaka, Adachi Yasuhiro, Owada Yuji, Takayanagi Ryoichi, Inagaki Nobuya

DIABETES　64　A541　2015/06

ISSN： 0012-1797
Fatty Acid-Binding Protein 7 Regulates Function of Caveolae in Astrocytes through Expression of Caveolin-1 Peer-reviewed

Yoshiteru Kagawa, Yuki Yasumoto, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Hirofumi Miyazaki, Yui Yamamoto, Tomoo Sawada, Hiroko Kishi, Sei Kobayashi, Motoko Maekawa, Takeo Yoshikawa, Eiichi Takaki, Akira Nakai, Hiroshi Kogo, Toyoshi Fujimoto, Yuji Owada

GLIA　63　(5)　780-794　2015/05

DOI： 10.1002/glia.22784 　

ISSN： 0894-1491

eISSN： 1098-1136
A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts Peer-reviewed

Satoshi Shirao, Hiroshi Yoneda, Mizuya Shinoyama, Kazutaka Sugimoto, Hiroyasu Koizumi, Hideyuki Ishihara, Fumiaki Oka, Hirokazu Sadahiro, Sadahiro Nomura, Masami Fujii, Masakatsu Tamechika, Yoshiteru Kagawa, Yuji Owada, Michiyasu Suzuki

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM　35　(5)　835-842　2015/05

DOI： 10.1038/jcbfm.2014.260 　

ISSN： 0271-678X

eISSN： 1559-7016
脂肪酸結合タンパク5(FABP5)は胆汁の作用を介したK細胞における脂肪誘導性GIP分泌の制御に関与する

渋江公尊, 山根俊介, 原田範雄, 濱崎暁洋, 鈴木和代, 城尾恵里奈, 岩崎可南子, ダニエラ・ナステスカ, 原田貴成, 安達泰弘, 大和田祐二, 高柳涼一, 稲垣暢也

糖尿病　58　(Suppl.1)　S-128　2015/04
Publisher: (一社)日本糖尿病学会
ISSN： 0021-437X

eISSN： 1881-588X
Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion Peer-reviewed

Kimitaka Shibue, Shunsuke Yamane, Norio Harada, Akihiro Hamasaki, Kazuyo Suzuki, Erina Joo, Kanako Iwasaki, Daniela Nasteska, Takanari Harada, Yoshitaka Hayashi, Yasuhiro Adachi, Yuji Owada, Ryoichi Takayanagi, Nobuya Inagaki

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM　308　(7)　E583-E591　2015/04

DOI： 10.1152/ajpendo.00543.2014 　

ISSN： 0193-1849

eISSN： 1522-1555
Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies (vol 23, pg 6495, 2014) Peer-reviewed

Chie Shimamoto, Tetsuo Ohnishi, Motoko Maekawa, Akiko Watanabe, Hisako Ohba, Ryoichi Arai, Yoshimi Iwayama, Yasuko Hisano, Tomoko Toyota, Manabu Toyoshima, Katsuaki Suzuki, Yukihiko Shirayama, Kazuhiko Nakamura, Norio Mori, Yuji Owada, Tetsuyuki Kobayashi, Takeo Yoshikawa

HUMAN MOLECULAR GENETICS　24　(8)　2409-2409　2015/04

DOI： 10.1093/hmg/ddv011 　

ISSN： 0964-6906

eISSN： 1460-2083
Immunohistochemical analysis of sustentacular cells in the adrenal medulla, carotid body and sympathetic ganglion of mice using an antibody against brain-type fatty acid binding protein (B-FABP) Peer-reviewed

Sawetree Pakkarato, Surang Chomphoo, Yoshiteru Kagawa, Yuji Owada, Wilaiwan Mothong, Sitthichai Iamsaard, Tarinee Sawatpanich, Hisatake Kondo, Wiphawi Hipkaeo

JOURNAL OF ANATOMY　226　(4)　348-353　2015/04

DOI： 10.1111/joa.12285 　

ISSN： 0021-8782

eISSN： 1469-7580
Proteomic differential display analysis reveals decreased expression of PEA-15 and vimentin in FABP7-deficient astrocytes. Peer-reviewed

Ebrahimi M, Sharifi K, Islam A, Miyazaki H, Yasumoto Y, Kagawa Y, Yamamoto Y, Kitagawa T, Kuramitsu Y, Nakamura K, Owada Y

J Proteom Bioinform　8　9-14　2015
Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies Peer-reviewed

Chie Shimamoto, Tetsuo Ohnishi, Motoko Maekawa, Akiko Watanabe, Hisako Ohba, Ryoichi Arai, Yoshimi Iwayama, Yasuko Hisano, Tomoko Toyota, Manabu Toyoshima, Katsuaki Suzuki, Yukihiko Shirayama, Kazuhiko Nakamura, Norio Mori, Yuji Owada, Tetsuyuki Kobayashi, Takeo Yoshikawa

HUMAN MOLECULAR GENETICS　23　(24)　6495-6511　2014/12

DOI： 10.1093/hmg/ddu369 　

ISSN： 0964-6906

eISSN： 1460-2083
Expression of epidermal fatty acid binding protein (E-FABP) in septoclasts in the growth plate cartilage of mice Peer-reviewed

Yasuhiko Bando, Miyuki Yamamoto, Koji Sakiyama, Katsuyuki Inoue, Shota Takizawa, Yuji Owada, Shoichi Iseki, Hisatake Kondo, Osamu Amano

JOURNAL OF MOLECULAR HISTOLOGY　45　(5)　507-518　2014/10

DOI： 10.1007/s10735-014-9576-1 　

ISSN： 1567-2379

eISSN： 1567-2387
Fatty Acid Binding Protein 3 Is Involved in n-3 and n-6 PUFA Transport in Mouse Trophoblasts Peer-reviewed

Ariful Islam, Yoshiteru Kagawa, Kazem Sharifi, Majid Ebrahimi, Hirofumi Miyazaki, Yuki Yasumoto, Saki Kawamura, Yui Yamamoto, Syuiti Sakaguti, Tomoo Sawada, Nobuko Tokuda, Norihiro Sugino, Ryoji Suzuki, Yuji Owada

JOURNAL OF NUTRITION　144　(10)　1509-1516　2014/10

DOI： 10.3945/jn.114.197202 　

ISSN： 0022-3166

eISSN： 1541-6100
Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury Peer-reviewed

Hirofumi Miyazaki, Tomoo Sawada, Miwa Kiyohira, Zhiqian Yu, Keiji Nakamura, Yuki Yasumoto, Yoshiteru Kagawa, Majid Ebrahimi, Ariful Islam, Kazem Sharifi, Saki Kawamura, Takanori Kodama, Yui Yamamoto, Yasuhiro Adachi, Nobuko Tokuda, Shuji Terai, Isao Sakaida, Toshizo Ishikawa, Yuji Owada

AMERICAN JOURNAL OF PATHOLOGY　184　(9)　2505-2515　2014/09

DOI： 10.1016/j.ajpath.2014.05.015 　

ISSN： 0002-9440

eISSN： 1525-2191
FABP3 Protein Promotes alpha-Synuclein Oligomerization Associated with 1-Methyl-1,2,3,6-tetrahydropiridine-induced Neurotoxicity Peer-reviewed

Norifumi Shioda, Yasushi Yabuki, Yuka Kobayashi, Misaki Onozato, Yuji Owada, Kohji Fukunaga

JOURNAL OF BIOLOGICAL CHEMISTRY　289　(27)　18957-18965　2014/07

DOI： 10.1074/jbc.M113.527341 　

ISSN： 0021-9258

eISSN： 1083-351X
マウス脳からのニューロン及びアストロサイトの初代培養法 Peer-reviewed

香川慶輝, Majid Ebrahimi, 大和田祐二

山口医学　63　(2)　89-91　2014/05

DOI： 10.2342/ymj.63.89 　
Hyperlocomotor activity and stress vulnerability during adulthood Induced by social isolation after early weaning are prevented by voluntary running exercise before normal weaning period Peer-reviewed

Junko Ishikawa, Yuko Ogawa, Yuji Owada, Akinori Ishikawa

BEHAVIOURAL BRAIN RESEARCH　264　197-206　2014/05

DOI： 10.1016/j.bbr.2014.02.007 　

ISSN： 0166-4328

eISSN： 1872-7549
Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans Peer-reviewed

Sadahiro Nomura, Masami Fujii, Takao Inoue, Yeting He, Yuichi Maruta, Hiroyasu Koizumi, Eiichi Suehiro, Hirochika Imoto, Hideyuki Ishihara, Fumiaki Oka, Mishiya Matsumoto, Yuji Owada, Takeshi Yamakawa, Michiyasu Suzuki

EPILEPSIA　55　(5)　770-776　2014/05

DOI： 10.1111/epi.12600 　

ISSN： 0013-9580

eISSN： 1528-1167
Pathological features of highly invasive glioma stem cells in a mouse xenograft model Peer-reviewed

Hirokazu Sadahiro, Koichi Yoshikawa, Makoto Ideguchi, Koji Kajiwara, Aya Ishii, Eiji Ikeda, Yuji Owada, Yuki Yasumoto, Michiyasu Suzuki

BRAIN TUMOR PATHOLOGY　31　(2)　77-84　2014/04

DOI： 10.1007/s10014-013-0149-x 　

ISSN： 1433-7398

eISSN： 1861-387X
Preservation of cochlear function in Fabp3 (H-Fabp) knockout mice Peer-reviewed

Jun Suzuki, Takeshi Oshima, Naohiro Yoshida, Ryuichi Kimura, Yusuke Takata, Yuji Owada, Toshimitsu Kobayashi, Yukio Katori, Noriko Osumi

NEUROSCIENCE RESEARCH　81-82　64-68　2014/04

DOI： 10.1016/j.neures.2014.02.003 　

ISSN： 0168-0102

eISSN： 1872-8111
Spinal cord ischemia/injury Peer-reviewed

T. Ishikawa, H. Suzuki, K. Ishikawa, S. Yasuda, T. Matsui, M. Yamamoto, T. Kakeda, S. Yamamoto, Y. Owada, T. L. Yaksh

Current Pharmaceutical Design　20　(36)　5738-5743　2014/01/01
Publisher: Bentham Science Publishers B.V.
ISSN： 1873-4286 1381-6128
Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice Peer-reviewed

Fumie Kizuka-Shibuya, Nobuko Tokuda, Kiyoshi Takagi, Yasuhiro Adachi, Lifa Lee, Isao Tamura, Ryo Maekawa, Hiroshi Tamura, Takashi Suzuki, Yuji Owada, Norihiro Sugino

JOURNAL OF OVARIAN RESEARCH　7　10　2014/01

DOI： 10.1186/1757-2215-7-10 　

ISSN： 1757-2215
Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells Peer-reviewed

Kazem Sharifi, Majid Ebrahimi, Yoshiteru Kagawa, Ariful Islam, Tuerhong Tuerxun, Yuki Yasumoto, Tomonori Hara, Yui Yamamoto, Hirofumi Miyazaki, Nobuko Tokuda, Takeo Yoshikawa, Yuji Owada

CELL AND TISSUE RESEARCH　354　(3)　683-695　2013/12

DOI： 10.1007/s00441-013-1730-7 　

ISSN： 0302-766X

eISSN： 1432-0878
Fatty acid binding protein 7 as a marker of glioma stem cells Peer-reviewed

Yusuke Morihiro, Yuki Yasumoto, Linda Koshy Vaidyan, Hirokazu Sadahiro, Tomoyuki Uchida, Akinori Inamura, Kazem Sharifi, Makoto Ideguchi, Sadahiro Nomura, Nobuko Tokuda, Shoji Kashiwabara, Aya Ishii, Eiji Ikeda, Yuji Owada, Michiyasu Suzuki

PATHOLOGY INTERNATIONAL　63　(11)　546-553　2013/11

DOI： 10.1111/pin.12109 　

ISSN： 1320-5463

eISSN： 1440-1827
脳型脂肪酸結合蛋白質(FABP7)はcaveolin-1の発現を介して脂質ラフト形成を制御する Peer-reviewed

香川慶輝, Majid Ebrahimi, Kazem Sharifi, 安本有希, 宮崎啓史, Ariful Islam, 山本由似, 河村沙樹, 原伯徳, 澤田知夫, 大和田祐二

山口医学　62　(3)　172-173　2013/08
Publisher: 山口大学医学会
ISSN： 0513-1731

eISSN： 1880-4462
Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5. International-journal Peer-reviewed

Akinori Inamura, Yasuhiro Adachi, Takao Inoue, Yeting He, Nobuko Tokuda, Takashi Nawata, Satoshi Shirao, Sadahiro Nomura, Masami Fujii, Eiji Ikeda, Yuji Owada, Michiyasu Suzuki

Neurochemical research　38　(8)　1641-7　2013/08

DOI： 10.1007/s11064-013-1066-4 　

ISSN： 0364-3190

More details Close

The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.
The Effect of Hypothermia Therapy on Cortical Laminar Disruption following Ischemic Injury in Neonatal Mice Peer-reviewed

Hiroyuki Kida, Sadahiro Nomura, Mizuya Shinoyama, Makoto Ideguchi, Yuji Owada, Michiyasu Suzuki

PLOS ONE　8　(7)　e68877　2013/07

DOI： 10.1371/journal.pone.0068877 　

ISSN： 1932-6203
Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: Analysis from a neurophysiological perspective Peer-reviewed

Yeting He, Masami Fujii, Takao Inoue, Sadahiro Nomura, Yuichi Maruta, Fumiaki Oka, Satoshi Shirao, Yuji Owada, Hiroyuki Kida, Ichiro Kunitsugu, Toshitaka Yamakawa, Tatsuji Tokiwa, Takeshi Yamakawa, Michiyasu Suzuki

BRAIN RESEARCH　1497　53-60　2013/02

DOI： 10.1016/j.brainres.2012.11.041 　

ISSN： 0006-8993
Epidermal-type FABP is a predictive marker of clinical response to systemic treatment and ultraviolet therapy in psoriatic skin lesions Peer-reviewed

Tomomi Miyake, Eisaku Ogawa, Asuka Mikoshiba, Aya Kobayashi, Hiroaki Hosoe, Shoji Kashiwabara, Hisashi Uhara, Yuji Owada, Ryuhei Okuyama

JOURNAL OF DERMATOLOGICAL SCIENCE　68　(3)　199-202　2012/12

DOI： 10.1016/j.jdermsci.2012.09.002 　

ISSN： 0923-1811
霊長類を用いたけいれん誘発てんかんモデルに対する局所脳冷却と運動機能への抑制効

井上貴雄, 藤井正美, 木田裕之, 山川俊貴, 丸田雄一, 賀業霆, 常盤達司, 野村貞宏, 大和田祐二, 山川烈, 山川烈, 鈴木倫保, 井上貴雄, 藤井正美, 木田裕之, 山川俊貴, 丸田雄一, 賀業霆, 常盤達司, 野村貞宏, 大和田祐二, 山川烈, 鈴木倫保

てんかん研究　30　(2)　327　2012/09/30

ISSN： 0912-0890
FATTY ACID BINDING PROTEIN 3 (FABP3) AS A CELLULAR REGULATOR OF FATTY ACID TRANSPORT FROM MOTHER TO FETUS IN RODENT PLACENTA Peer-reviewed

Ariful Islam, Nobuko Tokuda, Yasuhiro Adachi, Tomoo Sawada, Kazem Sharifi, Majid Ebrahimi, Ryoji Suzuki, Yuji Owada

PLACENTA　33　(9)　A28-A28　2012/09

ISSN： 0143-4004
Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in the mouse thymic epithelial cells Peer-reviewed

Yasuhiro Adachi, Sumie Hiramatsu, Nobuko Tokuda, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Yoshiteru Kagawa, Linda Koshy Vaidyan, Tomoo Sawada, Kimikazu Hamano, Yuji Owada

HISTOCHEMISTRY AND CELL BIOLOGY　138　(3)　397-406　2012/09

DOI： 10.1007/s00418-012-0963-y 　

ISSN： 0948-6143
Involvement of Bone Marrow-Derived Vascular Progenitor Cells in Neovascularization During Formation of the Corpus Luteum in Mice Peer-reviewed

Fumie Kizuka, Nobuko Tokuda, Kiyoshi Takagi, Yasuhiro Adachi, Lifa Lee, Isao Tamura, Ryo Maekawa, Toshiaki Taketani, Hiroshi Tamura, Takashi Suzuki, Yuji Owada, Norihiro Sugino

BIOLOGY OF REPRODUCTION　87　(3)　55　2012/09

DOI： 10.1095/biolreprod.112.099960 　

ISSN： 0006-3363
The Effects of Fabp7 and Fabp5 on Postnatal Hippocampal Neurogenesis in the Mouse Peer-reviewed

Miho Matsumata, Nobuyuki Sakayori, Motoko Maekawa, Yuji Owada, Takeo Yoshikawa, Noriko Osumi

STEM CELLS　30　(7)　1532-1543　2012/07

DOI： 10.1002/stem.1124 　

ISSN： 1066-5099

eISSN： 1549-4918
Reduced size of sebaceous gland and altered sebum lipid composition in mice lacking fatty acid binding protein 5 gene Peer-reviewed

Tomoko Sugawara, Kei Nemoto, Yasuhiro Adachi, Nozomi Yamano, Nobuko Tokuda, Masahiko Muto, Ryuhei Okuyama, Shingo Sakai, Yuji Owada

EXPERIMENTAL DERMATOLOGY　21　(7)　543-546　2012/07

DOI： 10.1111/j.1600-0625.2012.01514.x 　

ISSN： 0906-6705

eISSN： 1600-0625
FABP7欠損混合皮質培養におけるニューロン形態の変化(Altered morphology of neurons in FABP7-deficient mixed cortical culture)

Ebrahimi Majid, Kagawa Yoshiteru, Sharifi Kazem, Nawata Takashi, Adachi Yasuhiro, Sawada Tomoo, Tokuda Nobuko, Owada Yuji

解剖学雑誌　87　(2)　44-44　2012/06
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions Peer-reviewed

Masami Fujii, Takao Inoue, Sadahiro Nomura, Yuichi Maruta, Yeting He, Hiroyasu Koizumi, Satoshi Shirao, Yuji Owada, Ichiro Kunitsugu, Toshitaka Yamakawa, Tatsuji Tokiwa, Satoshi Ishizuka, Takeshi Yamakawa, Michiyasu Suzuki

EPILEPSIA　53　(3)　485-493　2012/03

DOI： 10.1111/j.1528-1167.2011.03388.x 　

ISSN： 0013-9580
Protective effects of focal brain cooling on photochemically-induced cerebral infarction

GA GYOTEI, INOUE TAKAO, MARUTA YUICHI, KIDA HIROYUKI, OKA SHIRO, NOMURA SADAHIRO, FUJII MASAMI, OWADA YUJI, YAMAKAWA TAKESHI, SUZUKI MICHIYASU

脳循環代謝　24　(1)　213　2012

ISSN： 0915-9401
FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferation Peer-reviewed

Kazem Sharifi, Yusuke Morihiro, Motoko Maekawa, Yuki Yasumoto, Hisae Hoshi, Yasuhiro Adachi, Tomoo Sawada, Nobuko Tokuda, Hisatake Kondo, Takeo Yoshikawa, Michiyasu Suzuki, Yuji Owada

HISTOCHEMISTRY AND CELL BIOLOGY　136　(5)　501-513　2011/11

DOI： 10.1007/s00418-011-0865-4 　

ISSN： 0948-6143
脂肪酸結合タンパク質(FABP7)は肝クッパー細胞(KC)の機能制御を介して肝傷害過程に関わる

清平美和, 宮崎啓史, 澤田知夫, 原田美紀, 安達泰弘, 徳田信子, 大和田祐二

山口医学　60　(3)　76-76　2011/06
Publisher: 山口大学医学会
ISSN： 0513-1731

eISSN： 1880-4462
Dopamine D2 receptor as a novel target molecule for heart-type fatty acid binding protein Peer-reviewed

Norifumi Shioda, Yui Yamamoto, Yuji Owada, Kohji Fukunaga

Japanese Journal of Neuropsychopharmacology　31　(3)　125-130　2011/06

ISSN： 1340-2544
Regulation of Dopaminergic Neuronal Activity by Heart-type Fatty Acid Binding Protein in the Brain Peer-reviewed

Yui Yamamoto, Norifumi Shioda, Yuji Owada, Kohji Fukunaga

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　131　(4)　497-501　2011/04

DOI： 10.1248/yakushi.131.497 　

ISSN： 0031-6903
脂肪酸結合タンパク質・FABP7はクッパー細胞および細胞の貪食活性の制御に関わる

澤田知夫, 宮崎啓史, 清平美和, 徳田信子, 安達泰弘, 大和田祐二

解剖学雑誌　86　(1)　19-19　2011/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Epidermal FABP (FABP5) Regulates Keratinocyte Differentiation by 13(S)-HODE-Mediated Activation of the NF-kappa B Signaling Pathway Peer-reviewed

Eisaku Ogawa, Yuji Owada, Shuntaro Ikawa, Yasuhiro Adachi, Teie Egawa, Kei Nemoto, Kaori Suzuki, Takanori Hishinuma, Hiroshi Kawashima, Hisatake Kondo, Masahiko Muto, Setsuya Aiba, Ryuhei Okuyama

JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　(3)　604-612　2011/03

DOI： 10.1038/jid.2010.342 　

ISSN： 0022-202X
Errata: Regulation of Dopaminergic Neuronal Activity by Heart-type Fatty Acid Binding Protein in the Brain

YAMAMOTO Yui, SHIODA Norifumi, OWADA Yuji, FUKUNAGA Kohji

YAKUGAKU ZASSHI　131　(5)　862-862　2011
Publisher: The Pharmaceutical Society of Japan
DOI： 10.1248/yakushi.131.862 　

ISSN： 0031-6903
A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. International-journal Peer-reviewed

Fumiaki Kamada, Yoko Aoki, Ayumi Narisawa, Yu Abe, Shoko Komatsuzaki, Atsuo Kikuchi, Junko Kanno, Tetsuya Niihori, Masao Ono, Naoto Ishii, Yuji Owada, Miki Fujimura, Yoichi Mashimo, Yoichi Suzuki, Akira Hata, Shigeru Tsuchiya, Teiji Tominaga, Yoichi Matsubara, Shigeo Kure

Journal of human genetics　56　(1)　34-40　2011/01

DOI： 10.1038/jhg.2010.132 　

ISSN： 1434-5161

More details Close

Moyamoya disease (MMD) shows progressive cerebral angiopathy characterized by bilateral internal carotid artery stenosis and abnormal collateral vessels. Although ∼ 15% of MMD cases are familial, the MMD gene(s) remain unknown. A genome-wide association study of 785,720 single-nucleotide polymorphisms (SNPs) was performed, comparing 72 Japanese MMD patients with 45 Japanese controls and resulting in a strong association of chromosome 17q25-ter with MMD risk. This result was further confirmed by a locus-specific association study using 335 SNPs in the 17q25-ter region. A single haplotype consisting of seven SNPs at the RNF213 locus was tightly associated with MMD (P = 5.3 × 10(-10)). RNF213 encodes a really interesting new gene finger protein with an AAA ATPase domain and is abundantly expressed in spleen and leukocytes. An RNA in situ hybridization analysis of mouse tissues indicated that mature lymphocytes express higher levels of Rnf213 mRNA than their immature counterparts. Mutational analysis of RNF213 revealed a founder mutation, p.R4859K, in 95% of MMD families, 73% of non-familial MMD cases and 1.4% of controls; this mutation greatly increases the risk of MMD (P = 1.2 × 10(-43), odds ratio = 190.8, 95% confidence interval = 71.7-507.9). Three additional missense mutations were identified in the p.R4859K-negative patients. These results indicate that RNF213 is the first identified susceptibility gene for MMD.
Role of Polyunsaturated Fatty Acids and Fatty Acid Binding Protein in the Pathogenesis of Schizophrenia Peer-reviewed

Motoko Maekawa, Yuji Owada, Takeo Yoshikawa

CURRENT PHARMACEUTICAL DESIGN　17　(2)　168-175　2011/01

DOI： 10.2174/138161211795049615 　

ISSN： 1381-6128
Identification of FABP7 in fibroblastic reticular cells of mouse lymph nodes Peer-reviewed

Nobuko Tokuda, Toshiaki Adachi, Yasuhiro Adachi, Mayumi Higashi, Kazem Sharifi, Tuerhong Tuerxun, Tomoo Sawada, Hisatake Kondo, Yuji Owada

HISTOCHEMISTRY AND CELL BIOLOGY　134　(5)　445-452　2010/11

DOI： 10.1007/s00418-010-0754-2 　

ISSN： 0948-6143
表皮細胞の分化における表皮型脂肪酸結合タンパク(FABP5)の関与

安達泰弘, 根本圭, 徳田信子, 澤田知夫, 大和田祐二

解剖学雑誌　85　(2)　82-82　2010/06
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
FABP7の肝傷害過程における発現の意義

徳田信子, 澤田知夫, 中村啓二, 中原有海, 清平美和, 安達泰弘, 大和田祐二

解剖学雑誌　85　(2)　82-82　2010/06
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
リンパ節内の脂肪酸結合蛋白質(FABP)サブタイプの局在解析

徳田信子, 東麻由美, 安達利昭, 安達泰弘, 澤田知夫, 大和田祐二

解剖学雑誌　85　(Suppl.)　124-124　2010/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
マウス胸腺上皮細胞での液性因子産生における脂肪細胞型脂肪酸結合タンパク質(FABP4)の機能

安達泰弘, 平松澄恵, 徳田信子, 澤田知夫, 大和田祐二

解剖学雑誌　85　(Suppl.)　159-159　2010/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
脳型脂肪酸結合タンパク質(FABP7)のアストロサイトにおける機能 Peer-reviewed

安本有希, Kazem Sharifi, 森廣雄介, 安達泰弘, 徳田信子, 澤田知夫, 大和田祐二

解剖学雑誌　85　(Suppl.)　200-200　2010/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects Peer-reviewed

Motoko Maekawa, Yoshimi Iwayama, Ryoichi Arai, Kazuhiko Nakamura, Tetsuo Ohnishi, Tomoko Toyota, Masatsugu Tsujii, Yuji Okazaki, Noriko Osumi, Yuji Owada, Norio Mori, Takeo Yoshikawa

JOURNAL OF HUMAN GENETICS　55　(2)　127-130　2010/02

DOI： 10.1038/jhg.2009.133 　

ISSN： 1434-5161

eISSN： 1435-232X
Heart-Type Fatty Acid Binding Protein Regulates Dopamine D-2 Receptor Function in Mouse Brain Peer-reviewed

Norifumi Shioda, Yui Yamamoto, Masahiko Watanabe, Bert Binas, Yuji Owada, Kohji Fukunaga

JOURNAL OF NEUROSCIENCE　30　(8)　3146-3155　2010/02

DOI： 10.1523/JNEUROSCI.4140-09.2010 　

ISSN： 0270-6474
【広範囲血液・尿化学検査免疫学的検査[第7版] その数値をどう読むか】生化学的検査脂質関係脂肪酸結合蛋白質

徳田信子, 安達泰弘, 澤田知夫, 大和田祐二

日本臨床　68　(増刊1 広範囲血液・尿化学検査免疫学的検査(2))　80-82　2010/01
Publisher: (株)日本臨床社
ISSN： 0047-1852
Localization of fatty acid binding proteins (FABPs) in the cochlea of mice Peer-reviewed

Sachiko Saino-Saito, Ryoji Suzuki, Nobuko Tokuda, Hiroshi Abe, Hisatake Kondo, Yuji Owada

ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER　192　(4)　210-214　2010

DOI： 10.1016/j.aanat.2010.06.007 　

ISSN： 0940-9602
Localization of fatty acid binding protein of epidermal type common to dendritic cells and presumptive macrophages in Peyer's patches and epithelial M cells of mouse intestine Peer-reviewed

Ryoji Suzuki, Mohammad Reza Nourani, Sachiko Saino-Saito, Hiroshi Abe, Tomonori Nochi, Hiroshi Kiyono, Friedrich Spener, Hisatake Kondo, Yuji Owada

HISTOCHEMISTRY AND CELL BIOLOGY　132　(6)　577-584　2009/12

DOI： 10.1007/s00418-009-0638-5 　

ISSN： 0948-6143
Discrete localization of various fatty-acid-binding proteins in various cell populations of mouse retina Peer-reviewed

Sachiko Saino-Saito, Reza Mohammad Nourani, Hiroo Iwasa, Hisatake Kondo, Yuji Owada

CELL AND TISSUE RESEARCH　338　(2)　191-201　2009/11

DOI： 10.1007/s00441-009-0862-2 　

ISSN： 0302-766X
Platform presentations. Peer-reviewed

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Surgical and radiologic anatomy : SRA　31 Suppl 1　49-93　2009/09

DOI： 10.1007/BF03371485 　

ISSN： 0930-1038
表皮細胞の分化における表皮型脂肪酸結合タンパク質の関与

根本圭, 奥山隆平, 安達泰弘, 徳田信子, 澤田知夫, 大和田祐二, 武藤正彦

山口医学　58　(3)　125-125　2009/06
Publisher: 山口大学医学会
ISSN： 0513-1731

eISSN： 1880-4462
アストロサイトの分裂における脳型脂肪酸結合タンパク(FABP7)の関与 Peer-reviewed

森廣雄介, 安本有希, 徳田信子, 安達泰弘, 澤田知夫, 大和田祐二, 鈴木倫保

山口医学　58　(3)　125-125　2009/06
Publisher: 山口大学医学会
ISSN： 0513-1731

eISSN： 1880-4462
Arachidonic Acid Drives Postnatal Neurogenesis and Elicits a Beneficial Effect on Prepulse Inhibition, a Biological Trait of Psychiatric Illnesses Peer-reviewed

Motoko Maekawa, Noriko Takashima, Miho Matsumata, Shiro Ikegami, Masanori Kontani, Yoshinobu Hara, Hiroshi Kawashima, Yuji Owada, Yoshinobu Kiso, Takeo Yoshikawa, Kaoru Inokuchi, Noriko Osumi

PLOS ONE　4　(4)　e5085　2009/04

DOI： 10.1371/journal.pone.0005085 　

ISSN： 1932-6203
脳型脂肪酸結合タンパク(B-FABP/FABP7)は末梢免疫臓器のTRC(T zone reticular cells)に局在する

徳田信子, 安達利昭, 安達泰弘, 澤田知夫, 大和田祐二

解剖学雑誌　84　(Suppl.)　142-142　2009/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
マウス胸腺ナース細胞における脂肪細胞型脂肪酸結合タンパク(A-FABP/FABP4)の局在

安達泰弘, 平松澄恵, 徳田信子, 澤田知夫, 大和田祐二

解剖学雑誌　84　(Suppl.)　222-222　2009/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Cysteinyl Leukotrienes Enhance the Degranulation of Bone Marrow-Derived Mast Cells through the Autocrine Mechanism Peer-reviewed

Izumi Kaneko, Kaori Suzuki, Kaori Matsuo, Hiroyuki Kumagai, Yuji Owada, Naoya Noguchi, Takanori Hishinuma, Masao Ono

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　217　(3)　185-191　2009/03

DOI： 10.1620/tjem.217.185 　

ISSN： 0040-8727

eISSN： 1349-3329
Role of Heart-type Fatty Acid Binding Protein in the Brain Function Peer-reviewed

Keiju Motohashi, Yui Yamamoto, Norifumi Shioda, Hisatake Kondo, Yuji Owada, Kohji Fukunaga

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　129　(2)　191-195　2009/02

DOI： 10.1248/yakushi.129.191 　

ISSN： 0031-6903
Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration Peer-reviewed

Keiichi Tamai, Masafumi Toyoshima, Nobuyuki Tanaka, Noriko Yamamoto, Yuji Owada, Hiroshi Kiyonari, Kazuko Murata, Yoshiyuki Ueno, Masao Ono, Tooru Shimosegawa, Nobuo Yaegashi, Masahiko Watanabe, Kazuo Sugamura

AMERICAN JOURNAL OF PATHOLOGY　173　(6)　1806-1817　2008/12

DOI： 10.2353/ajpath.2008.080684 　

ISSN： 0002-9440

eISSN： 1525-2191
Mast cell hyperplasia in the skin of Dsg4-deficient hypotrichosis mice, which are long-living mutants of lupus-prone mice Peer-reviewed

Ming-Cai Zhang, Hiroshi Furukawa, Kazuhiro Tokunaka, Kan Saiga, Fumiko Date, Yuji Owada, Masato Nose, Masao Ono

IMMUNOGENETICS　60　(10)　599-607　2008/10

DOI： 10.1007/s00251-008-0320-4 　

ISSN： 0093-7711
Fatty acid-binding protein regulates LPS-induced TNF-alpha production in mast cells Peer-reviewed

Noriko Yamamoto, Izumi Kaneko, Keiju Motohashi, Hiroyuki Sakagami, Yasuhiro Adachi, Nobuko Tokuda, Tomoo Sawada, Hiroshi Furukawa, Yoshiya Ueyama, Kohji Fukunaga, Masao Ono, Hisatake Kondo, Yuji Owada

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS　79　(1-2)　21-26　2008/07

DOI： 10.1016/j.plefa.2008.06.003 　

ISSN： 0952-3278
心臓型脂肪酸結合タンパク質(H-FABP)の中枢神経系における機能解析

本橋慧樹, 北中のり子, 安達泰弘, 徳田信子, 澤田知夫, 福永浩司, 大和田祐二

解剖学雑誌　83　(2)　60-60　2008/06
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Activation of PPAR gamma reverses a defect of surfactant synthesis in mice lacking two types of fatty acid binding protein Peer-reviewed

Christian Schachtrup, Stefan Malcharek, Jack J. Haitsma, Burkhard Lachmann, Yuji Owada, Bert Binas, Hisatake Kondo, Bernd Ruestow, Hans-Joachim Galla, Friedrich Spener

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS　1781　(6-7)　314-320　2008/06

DOI： 10.1016/j.bbalip.2008.04.010 　

ISSN： 1388-1981
Activation of PPARgamma reverses a defect of surfactant synthesis in mice lacking two types of fatty acid binding protein. Peer-reviewed

Schachtrup C, Malcharek S, Haitsma JJ, Lachmann B, Owada Y, Binas B, Kondo H, Rüstow B, Galla HJ, Spener F

Biochimica et biophysica acta　1781　(6-7)　314-320　2008/06

DOI： 10.1016/j.bbalip.2008.04.010 　

ISSN： 0006-3002
Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype Peer-reviewed

Akiko Watanabe, Tomoko Toyota, Yuji Owada, Takeshi Hayashi, Yoshimi Iwayamal, Miho Matsumata, Akihiro Nakaya, Motoko Maekawa, Tetsuo Ohnishi, Ryoichi Arai, Katsuyasu Sakurai, Kazuo Yamada, Hisatake Kondo, Kenji Hashimoto, Noriko Osumi, Takeo Yoshikawa

BIOLOGICAL PSYCHIATRY　63　(7)　70S-70S　2008/04

ISSN： 0006-3223
高次脳機能における心臓型脂肪酸結合タンパク質(H-FABP/FABP3)の役割

本橋慧樹, 齋野幸子, 北中のり子, 安達泰弘, 徳田信子, 澤田知夫, 福永浩司, 近藤尚武, 大和田祐二

解剖学雑誌　83　(Suppl.)　147-147　2008/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
末梢性免疫臓器における脳型脂肪酸結合タンパク(B-FABP/FABP7)の局在

徳田信子, 安達泰弘, 澤田知夫, 大和田祐二

解剖学雑誌　83　(Suppl.)　157-157　2008/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
マウス胸腺における脂肪細胞型脂肪酸結合タンパク(A-FABP/FABP4)の局在

安達泰弘, 平松澄恵, 本橋慧樹, 北中のり子, 徳田信子, 澤田知夫, 近藤尚武, 大和田祐二

解剖学雑誌　83　(Suppl.)　238-238　2008/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Prostaglandin F-2 alpha regulates cytokine responses of mast cells through the receptors for prostaglandin E Peer-reviewed

Izumi Kaneko, Takanori Hishinuma, Kaori Suzuki, Yuji Owada, Noriko Kitanaka, Hisatake Kondo, Junichi Goto, Hiroshi Furukawa, Masao Ono

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　367　(3)　590-596　2008/03

DOI： 10.1016/j.bbrc.2008.01.002 　

ISSN： 0006-291X
Fatty acid binding protein: Localization and functional significance in the brain Peer-reviewed

Yuji Owada

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　214　(3)　213-220　2008/03

DOI： 10.1620/tjem.214.213 　

ISSN： 0040-8727

eISSN： 1349-3329
Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype Peer-reviewed

Akiko Watanabe, Tomoko Toyota, Yuji Owada, Takeshi Hayashi, Yoshimi Iwayama, Miho Matsumata, Yuichi Ishitsuka, Akihiro Nakaya, Motoko Maekawa, Tetsuo Ohnishi, Ryoichi Arai, Katsuyasu Sakurai, Kazuo Yamada, Hisatake Kondo, Kenji Hashimoto, Noriko Osumi, Takeo Yoshikawa

PLOS BIOLOGY　5　(11)　2469-2483　2007/11

DOI： 10.1371/journal.pbio.0050297 　

ISSN： 1544-9173
胸腺における脂肪酸結合タンパク(FABP)の発現解析

安達泰弘, 徳田信子, 澤田知夫, 大和田祐二

解剖学雑誌　82　(3)　114-114　2007/09
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Distinct developmental expression of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases and their involvement in hippocampal dendritic formation Peer-reviewed

Akifumi Kamata, Hiroyuki Sakagami, Hiroshi Tokumitsu, Masashi Sanda, Yuji Owada, Kohji Fukunaga, Hisatake Kondo

NEUROSCIENCE LETTERS　423　(2)　143-148　2007/08

DOI： 10.1016/j.neulet.2007.07.003 　

ISSN： 0304-3940
Enhanced expression of adipocyte-type fatty acid binding protein in murine lymphocytes in response to dexamethasone treatment Peer-reviewed

Soha Abdelkawi Abdelwahab, Yuji Owada, Noriko Kitanaka, Anne Adida, Hiroyuki Sakagami, Masao Ono, Makoto Watanabe, Friedrich Spener, Hisatake Kondo

MOLECULAR AND CELLULAR BIOCHEMISTRY　299　(1-2)　99-107　2007/05

DOI： 10.1007/s11010-005-9050-1 　

ISSN： 0300-8177
胸腺における脂肪酸結合タンパク(FABP)分子の発現解析

安達泰弘, 徳田信子, 澤田知夫, 近藤尚武, 大和田祐二

解剖学雑誌　82　(Suppl.)　262-262　2007/03
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: Possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling Peer-reviewed

Akiko Saito, Akira Sugawara, Akira Uruno, Masataka Kudo, Hiroyuki Kagechika, Yasufumi Sato, Yuji Owada, Hisatake Kondo, Mayumi Sato, Masahiko Kurabayashi, Masue Imaizumi, Shigeru Tsuchiya, Sadayoshi Ito

ENDOCRINOLOGY　148　(3)　1412-1423　2007/03

DOI： 10.1210/en.2006-0900 　

ISSN： 0013-7227
Somatodendritic localization of EFA6A, a guanine nucleotide exchange factor for ADP-ribosylation factor 6, and its possible interaction with alpha-actinin in dendritic spines Peer-reviewed

Hiroyuki Sakagami, Takashi Honma, Jun Sukegawa, Yuji Owada, Teruyuki Yanagisawa, Hisatake Kondo

EUROPEAN JOURNAL OF NEUROSCIENCE　25　(3)　618-628　2007/02

DOI： 10.1111/j.1460-9568.2007.05345.x 　

ISSN： 0953-816X
Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth Peer-reviewed

Akifumi Kamata, Hiroyuki Sakagami, Hiroshi Tokumitsu, Yuji Owada, Kohji Fukunaga, Hisatake Kondo

NEUROSCIENCE RESEARCH　57　(1)　86-97　2007/01

DOI： 10.1016/j.neures.2006.09.013 　

ISSN： 0168-0102
Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene Peer-reviewed

Yuji Owada, Soha Abdelkawi Abdelwahab, Noriko Kitanaka, Hiroyuki Sakagami, Hiroshi Takano, Yoshinobu Sugitani, Minoru Sugawara, Hiroshi Kawashima, Yoshinobu Kiso, Jalal Izadi Mobarakeh, Kazuhiko Yanai, Kenya Kaneko, Hiroshi Sasaki, Hiroshi Kato, Sachiko Saino-Saito, Nozomu Matsumoto, Norio Akaike, Tetsuo Noda, Hisatake Kondo

EUROPEAN JOURNAL OF NEUROSCIENCE　24　(1)　175-187　2006/07

DOI： 10.1111/j.1460-9568.2006.04855.x 　

ISSN： 0953-816X
Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells Peer-reviewed

N Kitanaka, Y Owada, R Okuyama, H Sakagami, MR Nourani, S Aiba, H Furukawa, M Watanabe, M Ono, T Ohteki, H Kondo

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　345　(1)　459-466　2006/06

DOI： 10.1016/j.bbrc.2006.04.114 　

ISSN： 0006-291X
Distinct spatiotemporal expression of EFA6D, a guanine nucleotide exchange factor for ARF6, among the EFA6 family in mouse brain Peer-reviewed

Hiroyuki Sakagami, Hiroharu Suzuki, Akifumi Kamata, Yuji Owada, Kohji Fukunaya, Hideaki Mayanagi, Hisatake Kondo

BRAIN RESEARCH　1093　(1)　1-11　2006/06

DOI： 10.1016/j.brainres.2006.02.058 　

ISSN： 0006-8993
Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene Peer-reviewed

Y Kusakari, E Ogawa, Y Owada, N Kitanaka, H Watanabe, M Kimura, H Tagami, H Kondo, S Aiba, R Okuyama

MOLECULAR AND CELLULAR BIOCHEMISTRY　284　(1-2)　183-188　2006/03

DOI： 10.1007/s11010-005-9048-8 　

ISSN： 0300-8177
Localization of Ca/calmodulin-dependent protein kinase I in the carotid body chief cells and the ganglionic small intensely fluorescent (SIF) cells of adult rats Peer-reviewed

H Hoshi, H Sakagami, Y Owada, H Kondo

ARTERIAL CHEMORECEPTORS　580　87-92　2006

DOI： 10.1007/0-387-31311-7_13 　

ISSN： 0065-2598
Prominent expression and activity-dependent nuclear translocation of Ca2+/calmodulin-dependent protein kinase I delta in hippocampal neurons Peer-reviewed

H Sakagami, A Kamata, H Nishimura, J Kasahara, Y Owada, Y Takeuchi, M Watanabe, K Fukunaga, H Kondo

EUROPEAN JOURNAL OF NEUROSCIENCE　22　(11)　2697-2707　2005/12

DOI： 10.1111/j.1460-9568.2005.04463.x 　

ISSN： 0953-816X
Erratum: Cellular and subcellular localization of EFA6C, a third member of the EFA6 family, in adult mouse Purkinje cells (Journal of Neurochemistry (2005) 93 (674-85)) Peer-reviewed

Shigetsune Matsuya, Hiroyuki Sakagami, Akira Tohgo, Yuji Owada, Hye-Won Shin, Hiroshi Takeshima, Kazuhisa Nakayama, Shoichi Kokubun, Hisatake Kondo

Journal of Neurochemistry　95　(4)　1215　2005/11

DOI： 10.1111/j.1471-4159.2005.03421.x 　

ISSN： 0022-3042
Occurrence of immunoreactivity for adipocyte-type fatty acid binding protein in degenerating granulosa cells in atretic antral follicles of mouse ovary Peer-reviewed

Mohammad Reza Nourani, Yuji Owada, Noriko Kitanaka, Hiroyuki Sakagami, Hisae Hoshi, Hiroo Iwasa, Friedrich Spener, Hisatake Kondo

JOURNAL OF MOLECULAR HISTOLOGY　36　(8-9)　491-497　2005/10

DOI： 10.1007/s10735-006-9024-y 　

ISSN： 1567-2379
Localization of epidermal-type fatty acid binding protein in macrophages in advanced atretic follicles of adult mice Peer-reviewed

MR Nourani, Y Owada, N Kitanaka, SA Abdelwahab, H Iwasa, H Sakagami, F Spener, H Kondo

JOURNAL OF MOLECULAR HISTOLOGY　36　(6-7)　391-400　2005/09

DOI： 10.1007/s10735-005-9005-6 　

ISSN： 1567-2379
Cellular and subcellular localization of EFA6C, a third member of the EFA6 family, in adult mouse Purkinje cells Peer-reviewed

S Matsuya, H Sakagami, A Tohgo, Y Owada, HW Shin, H Takeshima, K Nakayama, S Kokubun, H Kondo

JOURNAL OF NEUROCHEMISTRY　93　(3)　674-685　2005/05

DOI： 10.1111/j.1471-4159.2005.03072.x 　

ISSN： 0022-3042
Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice Peer-reviewed

EJ Murphy, Y Owada, N Kitanaka, H Kondo, JFC Glatz

BIOCHEMISTRY　44　(16)　6350-6360　2005/04

DOI： 10.1021/bi047292r 　

ISSN： 0006-2960
Expression of liver-type fatty acid-binding protein in murine lung and its release into serum upon, challenge of lung with lipopolysaccharide Peer-reviewed

P Piumngam, C Schachtrup, Y Owada, H Kondo, C Promptmas, F Spener

EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY　107　(3)　145-152　2005/03

ISSN： 1438-7697
[Fatty acid binding proteins]. Peer-reviewed

Owada Y, Kitanaka N, Kondo H

Nihon rinsho. Japanese journal of clinical medicine　62 Suppl 12　95-97　2004/12

ISSN： 0047-1852
Differential localization of brain-type and epidermal-type fatty acid binding proteins in the adrenal gland of mice Peer-reviewed

Yun, X, MR Nourani, SA Abdelwahab, N Kitanaka, Y Owada, F Spener, H Iwasa, A Takahashi, H Kondo

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　203　(2)　77-86　2004/06

DOI： 10.1620/tjem.203.77 　

ISSN： 0040-8727

eISSN： 1349-3329
Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma. Peer-reviewed

Guthmann F, Schachtrup C, Tölle A, Wissel H, Binas B, Kondo H, Owada Y, Spener F, Rüstow B

Biochimica et biophysica acta　1636　(2-3)　196-204　2004/03

DOI： 10.1016/j.bbalip.2003.10.015 　

ISSN： 0006-3002
Specific localization of epidermal-type fatty acid binding protein in dendritic cells of splenic white pulp Peer-reviewed

N Kitanaka, Y Owada, SA Abdelwahab, H Iwasa, H Sakagami, M Watanabe, F Spener, H Kondo

HISTOCHEMISTRY AND CELL BIOLOGY　120　(6)　465-473　2003/12

DOI： 10.1007/s00418-003-0590-8 　

ISSN： 0948-6143
Localization of brain-type fatty acid-binding protein in Kupffer cells of mice and its transient decrease in response to lipopolysaccharide Peer-reviewed

SA Abdelwahab, Y Owada, N Kitanaka, H Iwasa, H Sakagami, H Kondo

HISTOCHEMISTRY AND CELL BIOLOGY　119　(6)　469-475　2003/06

DOI： 10.1007/s00418-003-0538-z 　

ISSN： 0948-6143
Cloning and characterization of a novel variant (mM-rdgB beta 1) of mouse M-rdgBs, mammalian homologs of Drosophila retinal degeneration B gene proteins, and its mRNA localization in mouse brain in comparison with other M-rdgBs Peer-reviewed

N Takano, Y Owada, R Suzuki, H Sakagami, T Shimosegawa, H Kondo

JOURNAL OF NEUROCHEMISTRY　84　(4)　829-839　2003/02

DOI： 10.1046/j.0022-3042.2003.01591.x 　

ISSN： 0022-3042
Analysis on the phenotype of E-FABP-gene knockout mice Peer-reviewed

Y Owada, Suzuki, I, T Noda, H Kondo

MOLECULAR AND CELLULAR BIOCHEMISTRY　239　(1-2)　83-86　2002/10

DOI： 10.1023/A:1020524621933 　

ISSN： 0300-8177
Altered water barrier function in epidermal-type fatty acid binding protein-deficient mice Peer-reviewed

Y Owada, H Takano, H Yamanaka, H Kobayashi, Y Sugitani, Y Tomioka, Suzuki, I, R Suzuki, T Terui, M Mizugaki, H Tagami, T Noda, H Kondo

JOURNAL OF INVESTIGATIVE DERMATOLOGY　118　(3)　430-435　2002/03

DOI： 10.1046/j.0022-202x.2001.01616.x 　

ISSN： 0022-202X
Localization of mRNAs for phosphatidylinositol phosphate kinases in the mouse brain during development. International-journal Peer-reviewed

Yosuke Akiba, Ryoji Suzuki, Sachiko Saito-Saino, Yuji Owada, Hiroyuki Sakagami, Makoto Watanabe, Hisatake Kondo

Brain research. Gene expression patterns　1　(2)　123-33　2002/01

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The gene expression for seven phosphatidylinositol phosphate kinases (PIPKs)-types Ialpha, Ibeta, Igamma, types IIalpha, IIbeta, IIgamma, and type III-was examined using in situ hybridization histochemistry, in the mouse brain during normal development. In the embryonic mouse brain, positive expression signals were detected only for the genes encoding PIPK Igamma and PIPK IIbeta in both the cerebral ventricular and mantle zones, with weaker signals in the former zone. On the other hand, the genes encoding all PIPKs were essentially detected in the external granule cell layer which represents the germinal zone for the neuronal granule cells. In the postnatal brain, among the seven PIPKs, the expression for genes encoding PIPK Igamma and IIbeta is evident in most gray matter, while the expression for the other five types was weak in the cortical gray matter and negligible in most non-cortical gray matter such as the diencephalon and brain stem nuclei. While the expression for most PIPKs in the mature hippocampus was distinct, the expression in the CA3 and the dentate gyrus was less definite for the genes encoding PIPK Ialpha and IIgamma, respectively. The distinct expression for the gene encoding PIPK IIalpha was detected in the postnatal white matter such as the cerebellar medulla, the corpus callosum, the hippocampal fimbriae, and the internal capsule.
Localization of epidermal-type fatty acid binding protein in the thymic epithelial cells of mice Peer-reviewed

Y Owada, R Suzuki, H Iwasa, F Spener, H Kondo

HISTOCHEMISTRY AND CELL BIOLOGY　117　(1)　55-60　2002/01

DOI： 10.1007/s00418-001-0354-2 　

ISSN： 0948-6143
Localization of mRNAs for subfamily of guanine nucleotide-exchange proteins (GEP) for ARFs (ADP-ribosylation factors) in the brain of developing and mature rats under normal and postaxotomy conditions Peer-reviewed

Suzuki, I, Y Owada, R Suzuki, T Yoshimoto, H Kondo

MOLECULAR BRAIN RESEARCH　98　(1-2)　41-50　2002/01

DOI： 10.1016/S0169-328X(01)00312-6 　

ISSN： 0169-328X
Structure and expression of the glycine cleavage system in rat central nervous system Peer-reviewed

Yoshiyuki Sakata, Yuji Owada, Kohji Sato, Kanako Kojima, Kinya Hisanaga, Toshikatsu Shinka, Yoichi Suzuki, Yoko Aoki, Jo Satoh, Hisatake Kondo, Yoichi Matsubara, Shigeo Kure

Molecular Brain Research　94　(1-2)　119-130　2001/10/19

DOI： 10.1016/S0169-328X(01)00225-X 　

ISSN： 0169-328X
Induction of mitochondrial heat shock protein 60 and 10 mRNAs following transient focal cerebral ischemia in the rat Peer-reviewed

Kenji Izaki, Hiroyuki Kinouchi, Katsuo Watanabe, Yuji Owada, Atsuya Okubo, Hideaki Itoh, Hisatake Kondo, Yohtalou Tashima, Shinya Tamura, Takashi Yoshimoto, Kazuo Mizoi

Molecular Brain Research　88　(1-2)　14-25　2001/03/31

DOI： 10.1016/S0169-328X(01)00012-2 　

ISSN： 0169-328X
Localization of mRNAs for six ARFs (ADP-ribosylation factors) in the brain of developing and adult rats and changes in the expression in the hypoglossal nucleus after its axotomy Peer-reviewed

Ichiro Suzuki, Yuji Owada, Ryoji Suzuki, Takashi Yoshimoto, Hisatake Kondo

Molecular Brain Research　88　(1-2)　124-134　2001/03/31

DOI： 10.1016/S0169-328X(01)00036-5 　

ISSN： 0169-328X
Localization of epidermal-type fatty acid binding protein in alveolar macrophages and some alveolar type II epithelial cells in mouse lung Peer-reviewed

Yuji Owada, Soha Abdelkawi Abdelwahab, Ryoji Suzuki, Hiroo Iwasa, Hiroyuki Sakagami, Friedrich Spener, Hisatake Kondo

Histochemical Journal　33　(8)　453-457　2001

DOI： 10.1023/A:1014420330284 　

ISSN： 0018-2214
Loss of neurons in the hippocampus and cerebral cortex of AMSH-deficient mice Peer-reviewed

N. Ishii, Y. Owada, M. Yamada, S. Miura, K. Murata, H. Asao, H. Kondo, K. Sugamura

Molecular and Cellular Biology　21　(24)　8626-8637　2001

DOI： 10.1128/MCB.21.24.8626-8637.2001 　

ISSN： 0270-7306
Simultaneous induction of mitochondrial heat shock protein mRNAs in rat forebrain ischemia Peer-reviewed

Atsuya Okubo, Hiroyuki Kinouchi, Yuji Owada, Hisanori Kunizuka, Hideaki Itoh, Kenji Izaki, Hisatake Kondo, Yohtalou Tashima, Takashi Yoshimoto, Kazuo Mizoi

Molecular Brain Research　84　(1-2)　127-134　2000/12/08

DOI： 10.1016/S0169-328X(00)00200-X 　

ISSN： 0169-328X
Localization of mRNA for SHIP2, SH2 domain-containing inositol polyphosphate 5-phosphatase, in the brain of developing and mature rats Peer-reviewed

Mutsuo Kudo, Sachiko Saito, Yuji Owada, Harumi Suzaki, Hisatake Kondo

Molecular Brain Research　75　(1)　172-177　2000/01/10

DOI： 10.1016/S0169-328X(99)00311-3 　

ISSN： 0169-328X
Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats Peer-reviewed

Hiromi Minami, Yuji Owada, Ryoji Suzuki, Yasunobu Handa, Hisatake Kondo

Journal of Molecular Neuroscience　15　(2)　121-135　2000

DOI： 10.1385/JMN:15:2:121 　

ISSN： 0895-8696
Localization of mRNA for Dri 42, subtype 2b of phosphatidic acid phosphatase, in the rat brain during development Peer-reviewed

Ryoji Suzuki, Hiroyuki Sakagami, Yuji Owada, Yasunobu Handa, Hisatake Kondo

Molecular Brain Research　66　(1-2)　195-199　1999/03/20

DOI： 10.1016/S0169-328X(99)00026-1 　

ISSN： 0169-328X
Localization of PDK-1 mRNA in the brain of developing and adult rats Peer-reviewed

S Yoshida, H Sakagami, Y Owada, S Kokubun, H Kondo

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　187　(3)　249-255　1999/03

ISSN： 0040-8727

eISSN： 1349-3329
脳におけるTRP(store-operated calcium channel)の遺伝子発現多様性

大塚祐司, 大和田祐二, 阪上洋行, 近藤尚武

解剖学雑誌　73　(4)　358-358　1998/08
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Differential Localization of mRNAs for Mammalian trps, Presumptive Capacitative Calcium Entry Channels, in the Adult Mouse Brain Peer-reviewed

Yuji Otsuka, Hiroyuki Sakagami, Yuji Owada, Hisatake Kondo

Tohoku Journal of Experimental Medicine　185　(2)　139-146　1998/06

DOI： 10.1620/tjem.185.139 　

ISSN： 0040-8727
A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration Peer-reviewed

Fuminori Ono, Tamotsu Nakagawa, Sachiko Saito, Yuji Owada, Hiroyuki Sakagami, Kaoru Goto, Masanori Suzuki, Seiki Matsuno, Hisatake Kondo

Journal of Biological Chemistry　273　(13)　7731-7736　1998/03/27

DOI： 10.1074/jbc.273.13.7731 　

ISSN： 0021-9258
Localization of mRNA for fatty acid transport protein in developing and mature brain of rats Peer-reviewed

Akihiro Utsunomiya, Yuji Owada, Takashi Yoshimoto, Hisatake Kondo

Molecular Brain Research　46　(1-2)　217-222　1997/06

DOI： 10.1016/S0169-328X(96)00303-8 　

ISSN： 0169-328X
Localization of gene expression for phosphatidylinositol transfer protein in the brain of developing and mature rats Peer-reviewed

Akihiro Utsunomiya, Yuji Owada, Takashi Yoshimoto, Hisatake Kondo

Molecular Brain Research　45　(2)　349-352　1997/05

DOI： 10.1016/S0169-328X(97)00030-2 　

ISSN： 0169-328X
Changes in gene expression for skin-type fatty acid binding protein in hypoglossal motor neurons following nerve crush Peer-reviewed

Yuji Owada, Akihiro Utsunomiya, Takashi Yoshimoto, Hisatake Kondo

Neuroscience Letters　223　(1)　25-28　1997/02/14

DOI： 10.1016/S0304-3940(97)13390-0 　

ISSN： 0304-3940
Expression of mRNA for Akt, Serine-Threonine Protein Kinase, in the Brain during Development and Its Transient Enhancement Following Axotomy of Hypoglossal Nerve Peer-reviewed

Yuji Owada, Akihiro Utsunomiya, Takashi Yoshimoto, Hisatake Kondo

Journal of Molecular Neuroscience　9　(1)　27-33　1997

DOI： 10.1007/BF02789392 　

ISSN： 0895-8696
Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains Peer-reviewed

Yuji Owada, Takashi Yoshimoto, Hisatake Kondo

Journal of Chemical Neuroanatomy　12　(2)　113-122　1996/12

DOI： 10.1016/S0891-0618(96)00192-5 　

ISSN： 0891-0618
Increased expression of the mRNA for brain- and skin-type but not heart-type fatty acid binding proteins following kainic acid systemic administration in the hippocampal glia of adult rats Peer-reviewed

Yuji Owada, Takashi Yoshimoto, Hisatake Kondo

Molecular Brain Research　42　(1)　156-160　1996/11

DOI： 10.1016/S0169-328X(96)00182-9 　

ISSN： 0169-328X
Induction of brain-derived neurotrophic factor (BDNF) and the receptor trk B mRNA following middle cerebral artery occlusion in rat Peer-reviewed

Shouichi Arai, Hiroyuki Kinouchi, Atsuya Akabane, Yuji Owada, Hideyuki Kamii, Makoto Kawase, Takashi Yoshimoto

Neuroscience Letters　211　(1)　57-60　1996/06/14

DOI： 10.1016/0304-3940(96)12720-8 　

ISSN： 0304-3940
Molecular cloning of rat cDNA for cytosolic phospholipase A<inf>2</inf> and the increased gene expression in the dentate gyrus following transient forebrain ischemia [Molecular Brain Research 25 (1994) 364-368] Peer-reviewed

Y. Owada, T. Tominaga, T. Yoshimoto, H. Kondo

Molecular Brain Research　27　(2)　355　1994/12

ISSN： 0169-328X
Molecular cloning of rat cDNA for cytosolic phospholipase A<inf>2</inf> and the increased gene expression in the dentate gyrus following transient forebrain ischemia Peer-reviewed

Yuji Owada, Teiji Tominaga, Takashi Yoshimoto, Hisatake Kondo

Molecular Brain Research　25　(3-4)　364-368　1994/09

DOI： 10.1016/0169-328X(94)90174-0 　

ISSN： 0169-328X
Localization of mRNA for β-adrenergic receptor kinase in the brain of adult rats Peer-reviewed

Yuji Owada, Masahiko Watanabe, Hisatake Kondo

Neuroscience Letters　144　(1-2)　9-13　1992/09/14

DOI： 10.1016/0304-3940(92)90704-B 　

ISSN： 0304-3940

Show all ︎Show first 5

Misc. 54

核内受容体PPARαに着目した統合失調症病態メカニズムの解明

前川素子, 和田唯奈, 吉町文子, 大西哲生, 吉川武男, 大和田祐二

日本解剖学会総会・全国学術集会講演プログラム・抄録集　127th (CD-ROM)　2022
The regulation mechanism of lipid raft function by Fatty Acid Binding Protein (FABP7)

Yoshiteru Kagawa, Yuji Owada

51　(14)　28-30　2019/12
Ndufs4欠損マウスにおける顎下腺・副腎の形態異常とステロイド合成障害

小林祐太, 本藏陽平, 阿部高明, 大和田祐二, 香取幸夫

耳鼻咽喉科ニューロサイエンス　33　38-41　2019/05
Publisher: 耳鼻咽喉科ニューロサイエンス研究会

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NDUFS4欠損マウスの顎下腺、副腎の組織学的評価を行い、電子伝達系がステロイド合成へ関与していることを示唆する所見を得たので報告した。マウスは(全身性)Ndufs4ノックアウトの雄を用いた。7週齢まで飼育し、顎下腺、精巣、副腎を採取して組織学的評価(Hematoxylin Eosin染色、免疫組織学的手法、Oil-Red O染色)を行った。同時に血液を採取し、血漿アンドロゲン濃度測定を行った。くわえて、マウスTM3細胞株(精巣Leydig細胞株、非腫瘍性)に対して免疫細胞染色、Western Blotを用いたNDUFS4発現評価を行った。Ndufs4ノックアウト雄マウスにおいて、顎下腺で、アンドロゲン依存性に線条部導管に好酸性顆粒を貯留した特殊な導管系(GCT)の著明な発達不良を認めた。この背景として、精巣には明らかな形態異常は認められなかったものの、血漿アンドロゲン濃度は明らかな低値傾向を示した。TM3細胞株において免疫細胞染色、Western BlotによるタンパクレベルでのNDUFS4の発現が確認された。くわえてNdufs4ノックアウト雄マウスにおいて、副腎皮質束状層でも形態学的異常を認めた。Oil-Red O染色の結果、精巣間質および副腎皮質において脂肪滴の減少〜枯渇をきたしていることが示唆された。
脂肪酸シグナリングに関与するFABP研究の新展開統合失調症と脂肪酸結合タンパク質

島本知英, 前川素子, 大西哲生, 豊田倫子, 岩山佳美, 大和田祐二, 吉川武男

日本生化学会大会プログラム・講演要旨集　91回　[1S10a-02]　2018/09
Publisher: (公社)日本生化学会
Fibroblastic Reticular Cells(FRC)におけるFABP7の局在と機能

徳田信子, 山本由似, 児玉孝憲, 徳田和央, 木村和博, 坂東康彦, 天野修, 宮崎啓史, 大和田祐二

日本解剖学会総会・全国学術集会講演プログラム・抄録集　123rd　2018
NDUFS4欠損マウスにおける顎下腺・副腎の形態異常とステロイド合成障害

小林祐太, 尾形雅君, 尾形雅君, 南都文香, 南都文香, 香川慶輝, 山本由似, 山本由似, 宮崎啓史, 伊藤将人, 香取幸夫, 阿部高明, 大和田祐二

日本解剖学会総会・全国学術集会講演プログラム・抄録集　123rd　133　2018
脂肪酸結合タンパク5(FABP5)の腸管内分泌K細胞における局在に関する検討

池口絵理, 渋江公尊, Thewjitcharoen Yotsapon, 山根俊介, 原田範雄, 原田貴成, 藤原雄太, 鈴木和代, 大和田祐二, 稲垣暢也

糖尿病　60　(Suppl.1)　S-262　2017/04
Publisher: (一社)日本糖尿病学会
ISSN： 0021-437X

eISSN： 1881-588X
Subcellular Translocation of Fatty Acid-Binding Protein 5 (FABP5) in Glucose-Dependent Insulinotropic Polypeptide (GIP)-Producing K-Cells: Re-Emerging Role of Transmission Electron Microscope

Kimitaka Shibue, Yotsapon Thewjitcharoen, Shunsuke Yamane, Norio Harada, Takanari Harada, Yuta Fujiwara, Kazuyo Suzuki, Yu Wang, Keiko Furuta, Yuji Owada, Nobuya Inagaki

ENDO2017　2017/04
質量分析法を用いた統合失調症関連脂質の探索

島本知英, 大西哲生, 江崎加代子, 前川素子, 渡辺明子, 豊島学, 杉山栄二, 大和田祐二, 瀬藤光利, 吉川武男

統合失調症研究　7　(1)　2017
Amelioration of PTSD-like Behavior by Melatonin in FABP3 Null Mice

Kohji Fukunaga, Yuji Owada, Ibuki Takahata, Yasushi Yabuki

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY　19　49-49　2016/06

ISSN： 1461-1457

eISSN： 1469-5111
免疫電顕法を用いた腸管内分泌K細胞の微細形態評価に関する研究

渋江公尊, Thewjitcharoen Yotsapon, 山根俊介, 原田範雄, 原田貴成, 藤原雄太, 鈴木和代, 大和田祐二, 稲垣暢也

糖尿病　59　(Suppl.1)　S-184　2016/04
Publisher: (一社)日本糖尿病学会
ISSN： 0021-437X

eISSN： 1881-588X
脂肪酸およびFABPと精神疾患の関連について

安本有希, 大和田祐二

日本疲労学会誌　11　(2)　18-25　2016/03
Publisher: 日本疲労学会

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脂肪酸結合蛋白質(FABP)は、哺乳類で11種類が同定されており、種々な組織や細胞に多様な発現を示す。神経系細胞におけるFABPをはじめとした脂質恒常性維持の分子メカニズムの解明により、精神疾患の新たな診断・予防・治療方法の確立に向けて道が拓かれることが期待されている。栄養と脳、体内脂質と精神疾患についての疫学的考察知見、脂肪酸輸送関連分子と精神疾患について述べた。
イメージング質量分析法を用いた統合失調症関連脂質の探索

島本知英, 大西哲生, 江崎加代子, 前川素子, 渡邉明子, 豊島学, 杉山栄二, 大和田祐二, 瀬藤光利, 吉川武男

日本分子生物学会年会プログラム・要旨集(Web)　39th　2016
統合失調症・自閉症スペクトラム障害の病態への脂肪酸結合タンパク質の関与

島本知英, 大西哲生, 前川素子, 豊田倫子, 渡辺明子, 豊島学, 鈴木勝昭, 中村和彦, 白山幸彦, 杉山栄二, 森則夫, 大和田祐二, 瀬戸光利, 小林哲幸, 吉川武男

統合失調症研究　6　(1)　2016
マウス小腸におけるIELの活性化および転帰の形態学的解析

尾形雅君, 香川慶輝, 安本有希, 宮崎啓史, 伊藤恒敏, 大和田祐二

Proceedings Clinical Electron Microscopy　35　13-17　2016
統合失調症・自閉症スペクトラム障害と脳に発現する脂肪酸結合タンパク質

島本知英, 島本知英, 大西哲生, 前川素子, 豊田倫子, 渡辺明子, 豊島学, 新井亮一, 鈴木勝昭, 中村和彦, 白山幸彦, 森則夫, 大和田祐二, 小林哲幸, 吉川武男

統合失調症研究　5　(1)　2015
脳型脂肪酸結合蛋白質によるアストロサイトの膜微小ドメイン機能制御

香川慶輝, 尾形雅君, Majid Ebrahimi, 大和田祐二

Proceedings Clinical Electron Microscopy　34　1-4　2015
脳に発現する脂肪酸結合タンパク質遺伝子ファミリーと精神疾患の関連性

島本知英, 大西哲生, 前川素子, 渡邊明子, 豊田倫子, 豊島学, 森則夫, 大和田祐二, 吉川武男

日本脳科学会プログラム・講演抄録集　41st　38-38　2014/11
Publisher: 日本脳科学会
FABP5 is an essential modulator of fatty acid-induced GIP secretion in enteroendocrine K cells

K. Shibue, S. Yamane, N. Harada, A. Hamasaki, K. Suzuki, E. Joo, K. Iwasaki, D. Nasteska, T. Harada, Y. Adachi, Y. Owada, R. Takayanagi, N. Inagaki

DIABETOLOGIA　57　S309-S310　2014/09

ISSN： 0012-186X

eISSN： 1432-0428
中枢神経系における活性温度帯の異なるTRPチャネルの発現・局在解析

FUJIYAMA YUICHI, KAGAWA YOSHITERU, KIDA HIROYUKI, NOMURA SADAHIRO, SUEHIRO EIICHI, INAMURA AKINORI, SHIBASAKI KOJI, OWADA YUJI, SUZUKI MICHIYASU

山口医学　63　(3)　232　2014/08/01

ISSN： 0513-1731
FABP3 promotes alpha-Syn oligomerization in dopaminergic neurons

Misaki Onozato, Norihumi Shioda, Yasushi Yabuki, Yuji Owada, Kohji Fukunaga

JOURNAL OF PHARMACOLOGICAL SCIENCES　124　143P-143P　2014

ISSN： 1347-8613

eISSN： 1347-8648
FABP3 regulates GABA signaling in cingulate cortical neurons

Yui Yamamoto, Kohji Fukunaga, Yuji Owada

JOURNAL OF PHARMACOLOGICAL SCIENCES　124　76P-76P　2014

ISSN： 1347-8613

eISSN： 1347-8648
脂肪酸結合タンパク質(Fabp)の蝸牛における機能解析加齢性難聴になりにくいマウスの発見

鈴木淳, 大島猛史, 吉田尚弘, 木村龍一, 吉崎嘉一, 高田雄介, 大和田祐二, 小林俊光, 大隅典子

日本抗加齢医学会総会プログラム・抄録集　13回　201-201　2013/06
Publisher: (一社)日本抗加齢医学会
The Relationship Between Cholesterol And Cerebral Vasospasm In A Rat Model Of Subarachnoid Hemorrhage: A Mechanistic Role For Lipid Rafts

Satoshi Shirao, Hiroshi Yoneda, Hideyuki Ishihara, Hiroko Yoshino, Kazutaka Sugimoto, Hiroyasu Koizumi, Eiichi Suehiro, Mizuya Shinoyama, Fumiaki Oka, Hirokazu Sadahiro, Sadahiro Nomura, Masami Fujii, Yoshiteru Kagawa, Yuji Owada, Michiyasu Suzuki

STROKE　44　(2)　2013/02

ISSN： 0039-2499

eISSN： 1524-4628
Fatty acid-binding protein 3 involved in neuronal transmission and emotional behavior

Yui Yamamoto, Yuji Owada, Kohji Fukunaga

JOURNAL OF PHARMACOLOGICAL SCIENCES　121　65P-65P　2013

ISSN： 1347-8613
脂肪酸結合タンパク質7型

徳田信子, 大和田祐二

脳科学辞典　2012/04/20

DOI： 10.14931/bsd.1102 　
全ゲノム関連解析による最初のもやもや病遺伝子 RNF213の同定

鎌田文顕, 青木洋子, 成澤あゆみ, 阿部裕, 小松崎匠子, 菅野潤子, 新堀哲也, 松原洋一, 呉繁夫, 菊池敦生, 土屋滋, 藤村幹, 冨永悌二, 小野栄夫, 石井直人, 大和田祐二, 真下陽一, 鈴木洋一, 羽田明

日本小児科学会雑誌　115　(9)　1478-1478　2011/09
Publisher: (公社)日本小児科学会
ISSN： 0001-6543
Verification of the effect of intrathecal baclofen therapy in a rat model of cerebral palsy-induced spasticity

NOMURA Sadahiro, KAGAWA Yoshiteru, FUJII Masami, SHINOYAMA Mizuya, IMOTO Hirochika, MARUTA Yuichi, INOUE Takao, KIDA Hiroyuki, IDA Yuika, SUZUKI Michiyasu, OWADA Yuji

50　(1)　52-53　2011/06/15

ISSN： 1344-9699
Fatty acid binding protein (Fabp7) is involved in the maintenance of neural stem/progenitor cells, survival of neurons and maturation of astrocytes

Ryousuke Tashiro, Nobuyuki Sakayori, Miho Matsumata, Yuji Owada, Yoshio Wakamatsu, Noriko Osumi

NEUROSCIENCE RESEARCH　71　E127-E127　2011

DOI： 10.1016/j.neures.2011.07.543 　

ISSN： 0168-0102
Expression of FABP7 in normal and injured brain cortex and its role in astrocyte proliferation

Kazem Sharifi, Yusuke Morihiro, Yuki Yasumoto, Motoko Maekawa, Majid Ebrahimi, Nobuko Tokuda, Takeo Yoshikawa, Yuji Owada

NEUROSCIENCE RESEARCH　71　E63-E64　2011

DOI： 10.1016/j.neures.2011.07.269 　

ISSN： 0168-0102
Disappearance of Epileptic Discharges and Seizures with Cryoprobe in Rat brains

Tatsuji Tokiwa, Lev Zimin, Yuji Owada, Hiroshi Fujioka, Takao Inoue, Masami Fujii, Satoru Ishizuka, Michiyasu Suzuki, Takeshi Yamakawa

Proceedings of the 29th International Epilepsy Congress(IEC2011)　651　2011
成体マウス海馬の神経新生及び機能における脂肪酸結合タンパク質FABPの役割(The role of FABPs in postnatal hippocampal neurogenesis and function)

松股美穂, 前川素子, 有銘預世布, 大和田祐二, 曽良一郎, 吉川武男, 大隅典子

神経化学　49　(2-3)　566-566　2010/08
Publisher: 日本神経化学会
ISSN： 0037-3796
脳の温度制御による治療について:医療機器開発の最先端から

藤岡裕士, 藤岡裕士, 藤井正美, 藤井正美, 野村貞宏, 野村貞宏, 井本浩哉, 井本浩哉, 小泉博靖, 小泉博靖, 末廣栄一, 末廣栄一, 山川俊貴, 山川俊貴, 斉藤俊, 梶原浩司, 梶原浩司, 大和田祐二, 大和田祐二, 山川烈, 山川烈, 鈴木倫保, 鈴木倫保

ファジィシステムシンポジウム講演論文集(CD-ROM)　26th　2010

ISSN： 1882-0212
The role of FABPs in postnatal hippocampal neurogenesis and function

Miho Matsumata, Motoko Maekawa, Yosefu Arime, Yuji Owada, Ichiro Sora, Takeo Yoshikawa, Noriko Osumi

NEUROSCIENCE RESEARCH　68　E171-E171　2010

DOI： 10.1016/j.neures.2010.07.2333 　

ISSN： 0168-0102
Functional role of the interaction of heart-type fatty acid binding protein with dopamine D2 receptor

Norifumi Shioda, Yui Yamamoto, Yuji Owada, Kohji Fukunaga

JOURNAL OF PHARMACOLOGICAL SCIENCES　112　110P-110P　2010

ISSN： 1347-8613
Heart-type fatty acid binding protein regulates dopamine D2 receptor function

Norifumi Shioda, Yui Yamamoto, Masahiko Watanabe, Yuji Owada, Kohji Fukunaga

NEUROSCIENCE RESEARCH　68　E56-E57　2010

DOI： 10.1016/j.neures.2010.07.018 　

ISSN： 0168-0102
9P-A-3 Identification of Epileptogenic Focus by Employing Softcomputing and Establishment of Minimally Invasive and Definitive Surgery : Interim Report

YAMAKAWA Takeshi, SUZUKI Michiyasu, OWADA Yuji, FUJII Masami, ISHIZUKA Satoru, HORIO Keiichi, TOKIWA Tatsuji, NOMURA Sadahiro, AOU Shuji, INOUE Takao, HIRAYAMA Yuya, KOGA Hiroaki

Proceedings of the Annual Conference of Biomedical Fuzzy Systems Association　23　(0)　7-8　2010
Publisher: バイオメディカル・ファジィ・システム学会
DOI： 10.24466/pacbfsa.23.0_7 　

ISSN： 1345-1510

More details Close

The current localization accuracy of the epileptogenc focus is not good and thus the extirpation of focus with significant margin causes the removal of normal brain and leads to the severe aftereffects such as restricted vision, motor dysfunction, disorder of memory, and so on. To cope with this problem, we should develop the technology of (1) detecting the epileptogenic focus, (2) necrotizing the epileptogenic focus excluding normal brain. In case of distributed focuses in the normal neuron networks, it causes the after effect to necrotize the distributed focuses. Thus we need to develop another technology of (3) cooling down but not freezing the distributed focuses to suppress the seizures after onset of epilepsy.
成体マウス海馬歯状回の神経新生における脂肪酸結合タンパク質FABPの役割

松股美穂, 前川素子, 大和田祐二, 吉川武男, 大隅典子

生化学　ROMBUNNO.2T15-2　2010

ISSN： 0037-1017
The role of fatty acid binding proteins and polyunsaturated fatty acids in hippocampal neurogenesis

Noriko Osumi, Miho Matsumata, Nobuyuki Sakayori, Motoko Maekawa, Takeo Yoshikawa, Yuji Owada, Masanori Kontani, Hiroshi Kawashima, Yoshinobu Kiso

MECHANISMS OF DEVELOPMENT　126　S240-S240　2009/08

DOI： 10.1016/j.mod.2009.06.624 　

ISSN： 0925-4773
Novel regulation of dopamine D2 receptor by heart-type fatty acid-binding protein

Kohji Fukunaga, Norifumi Shioda, Yui Yamamoto, Yuji Owada

JOURNAL OF PHARMACOLOGICAL SCIENCES　109　32P-32P　2009

ISSN： 1347-8613
Neuropharmacological phenotype of mice lacking heart-type fatty acid binding protein

Yui Yamarrioto, Keiju Motohashi, Norifumi Shioda, Yuji Owada, Kohji Fukunaga

JOURNAL OF PHARMACOLOGICAL SCIENCES　109　109P-109P　2009

ISSN： 1347-8613
神経化学と精神医学の融合による精神疾患病態解明・治療法開発モデルラットにおいてアラキドン酸は神経新生を増大させ、プレパレス抑制を回復させる(Arachidonic acid increases neurogenesis and restores prepulse inhibition deficits in model rats)

前川素子, 高嶋記子, 松股美穂, 池上司郎, 紺谷昌仙, 原芳伸, 河島洋, 大和田祐二, 吉川武男, 湯浅茂樹, 木曽良信, 井ノ口馨, 大隅典子

神経化学　47　(2-3)　207-207　2008/08
Publisher: 日本神経化学会
ISSN： 0037-3796
Identification of Epileptogenic Focus by Employing Softcomputing and Establishment of Minimally Invasive and Definitive Surgery

Yamakawa Takeshi, Grigorievich Zimin Lev, Ishizuka Satoru, Horio Keiichi, Suzuki Michiyasu, Owada Yuji, Fujii Masami, Nomura Sadahiro, Yamakawa Toshitaka

Proceedings of the Annual Conference of Biomedical Fuzzy Systems Association　21　(0)　12-15　2008
Publisher: バイオメディカル・ファジィ・システム学会
DOI： 10.24466/pacbfsa.21.0_12 　

ISSN： 1345-1510

More details Close

Epilepsy is a chronic brain disorder characterized by recurrent seizures. The seizure is shot down by the surgical removal of the region which is so called "epileptogenic focus ". However, the accuracy to detect the focus is not good (order of cm). Thus the extirpation of origin with significant margin causes the removal of healthy brain and leads to the severe aftereffects such as restricted vision, motor dysfunction, disorder of memory, and so on. To cope with this problem, we should develop the technology of (1) detecting the epileptogenic focus, and (2) necrotizing the epileptogenic focus excluding healthy brain by (a) colliquative necrosis with flash freezing or (b) cauterizing by focused laser beam.
成体マウス海馬歯状回の神経新生における脂肪酸結合タンパク質FABPの役割

松股美穂, 前川素子, 大和田祐二, 大隅典子

生化学　3T5-1　2008

ISSN： 0037-1017
生後海馬神経新生を制御する脂肪酸結合タンパク質の解析

前川素子, 松股美穂, 大和田祐二, 湯浅茂樹, 大隅典子

Inflamm Regen　27　(4)　385　2007/07/01

ISSN： 1880-9693
Polyunsaturated fatty acids promote proliferation of neural progenitor cells in the hippocampal dentate gyrus

M. Maekawa, M. Matsumata, Y. Owada, M. Kontani, Y. Hara, H. Kawashima, Y. Kis, S. Yuasa, N. Osumi

NEUROSCIENCE RESEARCH　58　S57-S57　2007

ISSN： 0168-0102
FABP7 is required for maintenance of neural stem/progenitor cells in the postnatal hippocampus

Motoko Maekawa, Miho Matsumata, Yuji Owada, Shigeki Yuasa, Noriko Osumi

NEUROSCIENCE RESEARCH　55　S241-S241　2006

ISSN： 0168-0102
Cellular and subcellular localization of EFA6C, a third member of the EFA6 family, in adult mouse Purkinje cells (vol 95, pg 1215, 2005)

S Matsuya, H Sakagami, A Tohgo, Y Owada, HW Shin, H Takeshima, K Nakayama, S Kokubun, H Kondo

JOURNAL OF NEUROCHEMISTRY　95　(4)　1215-1215　2005/11

DOI： 10.1111/j.1471-4159.2005.03421 　

ISSN： 0022-3042
Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPAR-gamma

F Guthmann, C Schachtrup, A Tolle, H Wissel, B Binas, H Kondo, Y Owada, F Spener, B Rustow

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS　1636　(2-3)　196-204　2004/03

DOI： 10.1016/j.bbalip,2003.10.015 　

ISSN： 1388-1981
マウス脳白質における3種のホスファチジルイノシトールキナーゼ分子の遺伝子発現について(Distinct gene expression of three isoforms of Phosphatidylinositol phosphate(PIP) kinase in the white matter after young adult stages of mice)

秋葉陽介, 鈴木良地, 大和田祐二, 近藤尚武

解剖学雑誌　76　(1)　124-124　2001/02
Publisher: (一社)日本解剖学会
ISSN： 0022-7722
Localization of mRNAs for novel and atypical as well as conventional protein kinese C (PKC) I soforms in the brain of developing and mature rats

H. Minami, R Suzuki, Y. Owada, Y. Handa, H. Kondo

J. Mol. Neurosc　14　125-136　2001
S II-3 脂肪酸結合蛋白の組織発現解析

大和田祐二, 野田哲生, 近藤尚武

日本組織細胞化学会総会プログラムおよび抄録集　(40)　61-61　1999
Publisher: 日本組織細胞化学会
MOLECULAR-CLONING OF RAT CDNA FOR CYTOSOLIC PHOSPHOLIPASE-A(2) AND THE INCREASED GENE-EXPRESSION IN THE DENTATE GYRUS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA (VOL 25, PG 364, 1994)

Y OWADA, T TOMINAGA, T YOSHIMOTO, H KONDO

MOLECULAR BRAIN RESEARCH　27　(2)　355-355　1994/12

ISSN： 0169-328X
1B-6) 下垂体腺腫における末梢免疫能の検討(北日本脳神経外科連合会, 第16回学術集会)

大和田祐二, 池田秀敏, 吉本高志, 鈴木倫保, 小川欣一, 藤原和則

新潟医学会雑誌　107　(1)　80-80　1993/01
Publisher: 新潟医学会
ISSN： 0029-0440

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Presentations 122

FABP7 protects astrocyte against ROS toxicity under ROS stress

Ariful Islam, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Yuji Owada

第123回日本解剖学会総会　2018
FABP3 in the anterior cingulate cortex mediates methylation status of gluatamic acid decarboxylase 67 promoter region.

Yui Yamamoto, Hiroyuki Kida, Dai Mitsushma, Keiju Kamijo, Yuji Owada, Kohji Fukunaga

18th World Congress of Basic and Clinical Pharmacology　2018
Role of FABP7 in astrocytes and its possibe association with psychiatric diseases.

Yuji Owada

59th International Symposium on "Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues" Symposium "Signaling and Disease"　2018
FABP5-KO マウスにおけるseptoclastの形態変化とPPARサブタイプの局在

坂東康彦, 坂下英, 崎山浩司, 徳田信子, 大和田祐二, 天野修

第123回日本解剖学会総会　2018
メッケル軟骨消失課程におけるセプトクラストの分布と形態の時間的変化

坂下英, 坂東康彦, 崎山浩司, 大和田祐二, 天野修

第123回日本解剖学会総会　2018
パイエル板表皮型脂肪酸結合タンパク質発現によるB細胞アポトーシス誘導

鈴木良地, 大和田祐二, 阿部寛

第123回日本解剖学会総会　2018
東北大学における献体実務の現状と展望

大和田祐二

篤志解剖全国連合会第48回総会合同研修会　2018
脂肪酸結合蛋白質FABP3による介在ニューロンのエピゲノム調節機構

山本由似, 木田裕之, 美津島大, 福永浩司, 尾形雅君, 上条桂樹, 大和田祐二

第123回日本解剖学会総会　2018
Ndufs4欠損マウスにおける顎下腺・副腎の形態異常とステロイド合成障害

小林祐太, 尾形雅君, 南都文香, 香川慶輝, 山本由似, 宮崎啓史, 伊藤将人, 香取幸夫, 阿部高明, 大和田祐二

第123回日本解剖学会総会　2018
ミトコンドリア呼吸鎖複合体I構成蛋白質Ndufs4がアストロサイトのミトコンドリア機能におよぼす役割

南都文香, Angelina Misiou, Subrata Kumar Shil, 阿部高明, 大和田祐二

第123回日本解剖学会総会　2018
手術手技研修運営−企業の関与における適切な利益相反マネジメント事例−

北田容章, 出澤真理, 大和田祐二

第123回日本解剖学会総会　2018
Fibroblastic reticular cells (FRC)におけるFABP7の局在と機能

徳田信子, 山本由似, 児玉孝憲, 徳田和央, 木村和博, 坂東康彦, 天野修, 宮崎啓史, 大和田祐二

第123回日本解剖学会総会　2018
マクロファージの細胞内代謝変化による抗炎症性機能活性化とFABP7の関与の検討

宮崎啓史, 宍戸愛, 安本有希, 香川慶輝, 大和田祐二

第123回日本解剖学会総会　2018
腸上皮細胞間リンパ球の活性化に伴う小腸絨毛上皮細胞の剥離機構

尾形雅君, 上条桂樹, 伊藤恒敏, 大和田祐二

第123回日本解剖学会総会　2018
アストロサイトにおける脂肪酸結合蛋白質FABP7の機能解析.

香川慶輝, 大和田祐二

第123回日本解剖学会総会シンポジウム「脂質ホメオスタシス制御による生体構造・機能と疾患」　2018
パイエル板胚中心における表皮型脂肪酸結合タンパク質の機能

鈴木良地, 大和田祐二, 板東良雄

日本解剖学会第64回東北・北海道連合支部学術集会　2018
脱髄疾患におけるFABP7の発現変化と病態生理への関与

宮崎啓史, 神里賢勇, 佐藤匠, 大和田祐二

日本解剖学会第64回東北・北海道連合支部学術集会　2018
脂肪酸結合タンパク質（FABP）を通して精神疾患を理解する

大和田祐二

第14回REDEEMシンポジウム　2018
脂肪酸結合タンパク質によるエピゲノム制御

大和田祐二

第91回日本生化学会大会シンポジウム「脂肪酸シグナリングに関与するFABP研究の新展開」　2018
脂肪酸結合タンパク質の細胞核局在がエピゲノム変化におよぼす影響

香川慶輝, 大和田祐二

第59回日本組織細胞化学会総会シンポジウム「遺伝子発現のエピジェネティック制御とその破綻」　2018
Significance of FABP7 and Ndufs4 in the regulation of astrocyte mitochondorial dynamics and fucntions.

Angelina Misiou, Fumika Nanto, Yoshiteru Kagawa, Takaaki Abe, Yuji Owada

Euro-Japan double degree program International Workshop　2017
Evaluating therapeutic effects of Mitochonic acid 5 on mitochondrial diseases in a mouse model of Leigh syndrome.

Fumika Nanto, Angelina Misiou, Takaaki Abe, Yuji Owada

Euro-Japan double degree program International Workshop　2017
Localization and function of FABP7 in T cell area fibroblastic retinular cells

Nobuko Tokuda, Hirofumi Miyazaki, Yui Yamamoto, Yuji Owada

7th Internationla Workshop of Kyoto T Cell Conference　2017
The possible role of hypothalamic fatty acid binding protein 7 in the cotrol of leptin sensitivity

Yuki Yasumoto, Yuji Owada

Section of Comparative Medicine, Special Seminar　2017
Abnormal neuronal activity in the basolateral amygdala mediates PTSD-like behaviors in FABP3 null mice

Yasushi Yabuki, Ibuki Takahata, Yuji Owada, Kohji Fukunaga

第40回日本神経科学大会　2017
FABP3 in the anterior cingulate cortex mediates methylation status of GAD67 promotor region

Yuji Owada, Yui Yamamoto, Hiroyuki Kida, Yuchio Yanagawa, Dai Mitsushima, Kohji Fukunaga

第40回日本神経科学大会　2017
Significance of Ndufs4 in the regulation of astrocyte mitochondrial dynamics and function

Angelina Misiou, Fumika Nannto, Subrata Kumar Shil, Takaaki Abe, Yuji Owada

第40回日本神経科学大会　2017
Role of FABP7 in astrocytes and its possible association with human psychiatric diseases

Yuji Owada

Protein Misfolding Diseases and Therapy 2017　2017
FABP7 is involved in M2 polarization of macrophages via mitochondrial fatty-acid oxidation.

Hirofumi Miyazaki, Ai Shishido, Yoshiteru Kagawa, Yuki Yasumoto, Fumika Nannto, Yuji Owada

第46回日本免疫学会学術集会　2017
脂肪酸結合蛋白質3(FABP3)は前帯状皮質においてGAD67プロモーターのメチル化を制御する

山本由似, 木田裕之, 美津島大, 大和田祐二, 福永浩司

第90回日本薬理学会年会　2017
マウス骨端板におけるseptoclastの発生と由来

坂東康彦, 坂下英, 崎山浩司, 大和田祐二, 天野修

第122回日本解剖学会総会　2017
パイエル板M細胞表皮型脂肪酸結合タンパク質発現による濾胞関連上皮内への樹状細胞遊走調節機構

鈴木良地, 大和田祐二, 阿部寛

第122回日本解剖学会総会　2017
FABP3はGAD67のプロモーター領域のメチル化状態を制御することで認知、情動行動に関与する

山本由似, 木田裕之, 美津島大, 澤田知夫, 福永浩司, 石田雄介, 上条桂樹, 大和田祐二

第122回日本解剖学会総会　2017
腸上皮細胞間リンパ球(IEL)の抗体刺激に伴う絨毛上皮細胞の剥離機構

尾形雅君, 香川慶輝, 安本有希, 伊藤恒敏, 大和田祐二

第122回日本解剖学会総会　2017
サージカルトレーニング運営ー問題点の克服と研究との両立ー

北田容章, 出澤真理, 大和田祐二

第122回日本解剖学会総会　2017
FABP7は視床下部アストロサイトにおけるレプチン感受性を調節し、高脂肪食摂取量を抑制する

安本有希, 宮崎啓史, 大和田祐二

第122回日本解剖学会総会　2017
Dab1は海馬体各領域の形態形成に異なる関与をする

Marissa Blume, 井之口文月, 瀧公介, 大和田祐二, 相良良成, 勝山裕

第122回日本解剖学会総会　2017
FABPによって制御される細胞内代謝がマクロファージ機能に及ぼす影響

宮崎啓史, 大和田祐二

第122回日本解剖学会総会　2017
細胞核内FABP7はcaveolin-1遺伝子発現をエピジェネティックに制御する

香川慶輝, Ariful Islam, 尾形雅君, 大和田祐二

第122回日本解剖学会総会　2017
脂肪酸結合蛋白質FABP7によるヒストンアセチル化を介したcaveolin-1転写調節機構

香川慶輝, 大和田祐二

第11回エピジェネティクス研究会年会　2017
ミトコンドリア呼吸鎖複合体I構成蛋白質Ndufs4がアストロサイトのミトコンドリア機能におよぼす動的変化および影響

南都文香, Angelina Misiou, Subrata Kumar Shil, 阿部高明, 大和田祐二

日本解剖学会第63回東北・北海道連合支部学術集会　2017
マクロファージの抗炎症性機能分化における細胞内代謝の変化とFABP7の関与

宮崎啓史, 宍戸愛, 香川慶輝, 安本有希, 南都文香, 大和田祐二

日本解剖学会第63回東北・北海道連合支部学術集会　2017
FABP7は核内Acetyl-CoAレベル調節を介してエピジェネティックに遺伝子発現を制御する

香川慶輝, 大和田祐二

第40回日本分子生物学会　2017
Ultimate fate of mouse small intestinal intra-epithelial lymphocytes

尾形雅君, 勝山裕, 香川慶輝, 伊藤恒敏, 大和田祐二

第121回日本解剖学会総会　2016
Possible role of hypothalamic FABP7 in the cotrol of glial cell proliferation and leptin sensitivity

Yasumoto Y, Owada Y

Cold Spring Harbor Laboratory Meeting - Glia in Health and Disease　2016
脂肪酸結合蛋白質3(FABP3)は前帯状皮質においてGAD67発現を制御する

山本由似, 木田裕之, 美津島大, 大和田祐二, 福永浩司

第89回日本薬理学会年会　2016
抑制性ニューロンにおける脂肪酸結合タンパク質FABP3の機能

山本由似, 木田裕之, 美津島大, 徳田信子, 澤田知夫, 福永浩司, 大和田祐二

第121回日本解剖学会総会　2016
大脳皮質特異的Dab1欠損マウスは精神疾患関連行動異常を示す

勝山裕, 今井英明, 昌子浩孝, 尾形雅君, 香川慶輝, 崎村健司, 宮川剛, 大和田祐二, 寺島俊雄

第121回日本解剖学会総会　2016
高脂肪食摂取肥満マウスにおける肝マクロファージのFABP7の機能的役割の検討

宮崎啓史, 児玉孝憲, 澤田知夫, 大和田祐二

第121回日本解剖学会総会　2016
マウス骨端板のseptoclastにおけるレチノイン酸欠乏・過剰による増殖抑制と形態変化

坂東康彦, 坂下英, 崎山浩司, 山本美由紀, 井関尚一, 大和田祐二, 天野修

第121回日本解剖学会総会　2016
マウスメッケル軟骨におけるseptoclastの分布と形態変化

坂下英, 坂東康彦, 崎山浩司, 大和田祐二, 天野修

第121回日本解剖学会総会　2016
パイエル板M細胞表皮型脂肪酸結合蛋白質発現による腸管粘膜免疫調節機構

鈴木良地, 大和田祐二, 阿部寛

第121回日本解剖学会総会　2016
脂肪酸結合蛋白質FABP7の細胞内局在変化がcaveolin-1遺伝子発現に及ぼす影響

香川慶輝, 大和田祐二

第121回日本解剖学会総会　2016
免疫電顕法をもちいた腸管内分泌Ｋ細胞の微細形態評価に関する研究

渋江公尊, Yotsapon Thewjitcharoen, 山根俊介, 原田範雄, 原田貴成, 藤原雄太, 鈴木和代, 大和田祐二, 稲垣暢也

第59回日本糖尿病学会学術集会　2016
神経系における組織・細胞形態解析の基礎と応用

大和田祐二

第41回組織細胞化学講習会　2016
脂肪酸結合蛋白質による前帯状皮質のGABAシステム制御

山本由似, 石田雄介, 上条桂樹, 福永浩司, 大和田祐二

生体機能と創薬シンポジウム2016　2016
脂肪酸結合蛋白質FABP7の細胞核局在の意義ーcaveolin-1遺伝子発現制御との関連ー

香川慶輝, Ariful Islam, 尾形雅君, 大和田祐二

第62回日本解剖学会東北・北海道連合支部学術集会　2016
腸上皮間リンパ球(IEL)における自己作用型DNA傷害およびDNA修復

尾形雅君, 香川慶輝, 安本有希, 伊藤恒敏, 大和田祐二

第62回日本解剖学会東北・北海道連合支部学術集会　2016
マウスパイエル板における粘膜下樹状細胞のfollicular associated epitheliumへの誘導

鈴木良地, 大和田祐二, 阿部寛

第62回日本解剖学会東北・北海道連合支部学術集会　2016
脂肪酸結合蛋白質は前帯状皮質のGABAシステムを制御する

山本由似, 石田雄介, 上条桂樹, 大和田祐二

第62回日本解剖学会東北・北海道連合支部学術集会　2016
視床下部グリアに発現するFABP7のレプチン感受性と摂食行動における機能

安本有希, 大和田祐二

第62回日本解剖学会東北・北海道連合支部学術集会　2016
前帯状皮質のGABAシステム制御機構における脂肪酸結合タンパク質の役割

山本由似, 福永浩司, 大和田祐二

第38回日本生物学的精神医学会　2016
脂肪酸結合蛋白質による神経可塑性制御と精神疾患病態への関与

大和田祐二

小児科イブニングカンファレンス　2016
核内FABP7はエピジェネティックなcaveolin-1の発現制御に関与する

香川慶輝, Ariful Islam, 尾形雅君, 大和田祐二

第39回日本分子生物学会年会　2016
Role of astrocyte-expressed FABP7 on morphology and synapse Formation of cortical neurons

Ebrahimi M, Kida H, Mitsushima D, Owada Y

第120回日本解剖学会総会・全国学術集会　2015
FABP7 is an epigenetic modulator of caveolin-1 gene expression in astrocytes

香川慶輝, 大和田祐二

第38回日本神経科学会　2015
Possible role of hypothalamic FABP7 in the cotrol of glial cell proliferation and leptin sensitivity

Yasumoto Y, Owada Y

Tools and Technologies, Frontiers of Brain Science, Tohoku Forum for Creativity　2015
Post-traumatic stress disorder-like behaviors in FABP3 null mice

福永浩司, 矢吹悌, 高畑伊吹, 大和田祐二

第42回日本脳科学会　2015
高脂肪食誘導脂肪性肝疾患モデルにおけるKupffer細胞のFABP7の機能的役割の検討

宮崎啓史, 児玉孝憲, 河村沙樹, 澤田知夫, 大和田祐二

第120回日本解剖学会総会・全国学術集会　2015
視床下部FABP7はグリアの分裂を制御し、摂食調節に関与する

安本有希, 宮崎啓史, 坂井基樹, 大和田祐二

第120回日本解剖学会総会・全国学術集会　2015
脳型脂肪酸結合蛋白質（FABP7)はマウスcaveolin-1遺伝子発現をエピジェネティックに制御する

香川慶輝, 向後寛, 岸博子, 小林誠, 藤本豊士, 大和田祐二

第120回日本解剖学会総会・全国学術集会　2015
脂肪酸結合蛋白質(FABP)を通して、栄養と精神疾患の関連を理解する

大和田祐二

第11回日本疲労学会総会・学術集会　2015
脂肪酸結合蛋白質の研究から疾患を理解する

大和田祐二

第100回東北医学会総会　2015
肪酸結合蛋白質によるグリア細胞の膜微小ドメイン制御

大和田祐二

第66回超微形態懇話会　2015
脂肪酸結合蛋白質による細胞膜微小ドメイン制御とその意義

大和田祐二

第11回必須脂肪酸と健康研究会　2015
アンモン角錐体ニューロンと歯状回顆粒ニューロンの前駆細胞は発生過程で混在する

勝山裕, 杉山拓, 大隅典子, 大和田祐二

第61回日本解剖学会東北・北海道連合支部会学術集会　2015
腸上皮細胞間リンパ球(IEL)の活性化および細胞死の形態学的解析

尾形雅君, 大和田祐二, 伊藤恒敏

第61回日本解剖学会東北・北海道連合支部会学術集会　2015
E-FABPによるパイエル板M細胞腸管内抗原取り込み機構制御

鈴木良地, 志村洋一郎, 徳田信子, 大和田祐二, 阿部寛

第61回日本解剖学会東北・北海道連合支部会学術集会　2015
FABP3遺伝子欠損マウスの認知・情動行動異常とメチオニンによる改善作用

山本由似, 木田裕之, 美津島大, 福永浩司, 大和田祐二

第37回日本生物学的精神医学会・第45回日本神経精神薬理学会　2015
マクロファージM1/M2分化におけるFABPの役割

児玉孝憲, 宮崎啓史, 澤田知夫, 大和田祐二, 徳田信子

第70回日本解剖学会中国・四国支部会学術集会　2015
脂肪酸結合蛋白質FABP3による抑制性介在神経制御機構

山本由似, 澤田知夫, 徳田信子, 大和田祐二

第70回日本解剖学会中国・四国支部会学術集会　2015
グリア細胞における脂肪酸結合蛋白質の機能−精神疾患との関連−

大和田祐二

第2回東北大学脳科学シンポジウム「脳高次機能と細胞内シグナル伝達」　2015
Fatty acid-binding protein 3 promotes α-Synuclein oligomerization

Norifumi Shioda, Yuji Owada, Kohji Fukunaga

International symposium "New Frontier of Molecular Neuropathology 2014"　2014
FABP3 regulates GABA signaling in cingulate cortical neurons

Yui Yamamoto, Kohji Fukunaga, Yuji Owada

第87回日本薬理学会年会　2014
ドパミン神経細胞において脂肪酸結合蛋白質はαシヌクレイン多量体形成を促進する

小野里美咲, 塩田倫史, 矢吹悌, 大和田祐二, 福永浩司

日本生化学会東北支部第80回例会・シンポジウム　2014
脂肪酸結合蛋白質FABP3はαシヌクレイン多量体形成を促進し、ドパミン神経細胞死に関与する

小野里美咲, 塩田倫史, 山口航矢, 矢吹悌, 大和田祐二, 福永浩司

第25回霧島神経薬理フォーラム　2014
脂肪酸結合蛋白質FABP3はαシヌクレイン多量体形成を促進する

塩田倫史, 大和田祐二, 福永浩司

生体機能と創薬シンポジウム　2014
FABP3 promotes MPTP-induced α-synuclein accumulations in dopaminergic neurons.

Yasushi Yabuki, Norifumi Shioda, Misaki Onozato, Yuji Owada, Kohji Fukunaga

The 8th Neurodegenerative Conditions Research & Development Conference　2014
FABP3 promotes α-synuclein oligomerization in dopaminergic neurons.

Kohji Fukunaga, Norifumi Shioda, Motohiro Morioka, Yuji Owada

Neuroscience 2014　2014
アラキドン酸はドパミン神経細胞におけるα-synuclein凝集を促進する

矢吹悌, 塩田倫史, 小野里美咲, 大和田祐二, 福永浩司

第44回日本神経精神薬理学会年会　2014
Fatty acid-binding protein 3 involved in neuronal transmission and emotional behavior （シグナル伝達と情動行動への脂肪酸結合蛋白質FABP3の関与）

山本由似, 大和田祐二, 福永浩司

第86回日本薬理学会年会　2013
Impaired cognitive function and anxiety-like behaviors in FABP3 null mice

Yui Yamamoto, Kohji Fukunaga, Yuji Owada

Neuro2013　2013
FABP3 aggravates α-synuclein accumulation in the dopaminergic neurons

Yasushi Yabuki, Norifumi Shioda, Yuka Kobayashi, Yuji Owada, Kohji Fukunaga

Neuro2013　2013
ドパミン神経細胞における脂肪酸結合蛋白質によるαシヌクレイン凝集体形成の分子機構

小野里美咲, 塩田倫史, 矢吹悌, 大和田祐二, 福永浩司

第86回日本生化学会大会　2013
FABP3 expression aggravates neuronal α-synuclein accumulation in Parkinson's model mice

Norifumi Shioda, Yasushi Yabuki, Yuji Owada, Kohji Fukunaga

第43th Society for Neuroscience; Annual Meeting　2013
統合失調症・自閉症で検出された脂肪酸結合タンパク質(FABP)変異の解析

島本知英, 大西哲生, 座古保, 大和田祐二, 小林哲幸, 吉川武男

第35回日本分子生物学会年会　2012
黒質ドパミン神経変性への脂肪酸結合タンパク質の関与

小林由佳, 塩田倫史, 大和田祐二, 福永浩司

生体機能と創薬シンポジウム 2012　2012
脂肪酸結合蛋白質FABP 欠損マウスにおける不安様行動とシグナル伝達異常

山本由似, 塩田倫史, 大和田裕二, 福永浩司

第42回日本神経精神薬理学会　2012
肪酸結合蛋白質FABP7によるクツパー細胞のサイトカイン産生制御

宮崎啓史, 津田知夫, 清平美和, 徳田信子, 安達泰弘, 大和田祐二

日本比較免疫学会第23回学術集会　2011
心臓型脂肪酸結合蛋白質欠損マウスの不安様行動の神経機序

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第20回日本臨床精神神経薬理学会第40回日本神経精神薬理学会合同年会　2011
脂肪酸結合蛋白質欠損マウスにおける不安様行動の脳内機構

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第62回日本薬理学会北部会　2011
心臓型脂肪酸結合蛋白質は中枢ドパミン神経活動を調節する.

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第130年会日本薬学会年会　2010
脂肪酸結合タンパク質によるドパミンD2受容体の制御機構

塩田倫史, 山本由似, 渡辺雅彦, 大和田祐二, 福永浩司

第53回日本神経化学会（Neuro2010）　2010
脂肪酸結合蛋白質によるドパミンD2受容体の機能調節

塩田倫史, 山本由似, 大和田祐二, 福永浩司

生体機能と創薬シンポジウム2010　2010
ドパミン D2受容体に対する脂肪酸結合蛋白質の機能的役割

塩田倫史, 山本由似, 大和田祐二, 福永浩司

次世代を担う創薬・医療薬理シンポジウム2010　2010
脂肪酸結合蛋白質欠損マウスにおけるハロペリドール誘導カタレプシー亢進の神経機序

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第20回日本臨床精神神経薬理学会・第40回日本神経精神薬理学会合同年会　2010
脂肪酸結合蛋白質欠損マウスにおけるアラキドン酸代謝と情動行動異常

福永浩司, 山本由似, 塩田倫史, 大和田祐二

第12回応用薬理シンポジウム　2010
心臓型脂肪酸結合蛋白質欠損マウスの神経薬理学的表現型.

山本由似, 本橋慧樹, 塩田倫史, 大和田祐二, 福永浩司

第82回日本薬理学会年会　2009
脂肪酸結合蛋白質によるドパミンD2受容体の新しい機能制御.

福永浩司, 塩田倫史, 山本由似, 大和田祐二

第82回日本薬理学会年会　2009
脂肪酸輸送タンパク質によるドパミン D2 受容体の制御機構.

塩田倫史, 山本由似, 大和田祐二, 福永浩司

第18回神経行動薬理若手研究者の集い　2009
脂肪酸結合タンパク質はドパミンD2受容体の機能調節に関与する.

塩田倫史, 大和田祐二, 山本由似, 福永浩司

日本生化学会東北支部第75回例会・シンポジウム　2009
脂肪酸結合蛋白質によるドパミン神経活動調節機構.

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第10回 Pharmaco-Hematologyシンポジウム　2009
心臓型脂肪酸結合蛋白質はドパミン神経活動を調節する.

山本由似, 塩田倫史, 大和田祐二, 福永浩司

第20回霧島神経薬理フォーラム　2009
脂肪酸結合タンパク質によるドパミンD2受容体機能調節.

塩田倫史, 山本由似, 大和田祐二, 福永浩司

第37回薬物活性シンポジウム　2009
Heart-type fatty acid binding protein regulates dopamine D2 receptor functions in mouse brain.

N. SHIODA, Y. YAMAMOTO, M. WATANABE, Y. OWADA, K. FUKUNAGA

Society for neuroscience, Neuroscience meeting 2009　2009
Critical role of interaction between H-FABP and dopamine D2 receptor in emotional behaviors.

K. FUKUNAGA, N. SHIODA, Y. YAMAMOTO, Y. OWADA

Society for neuroscience, Neuroscience meeting 2009　2009
脂肪酸結合蛋白質H-FABPによるドパミンD2受容体の機能調節.

塩田倫史, 山本由似, 大和田祐二, 福永浩司

第39回日本神経精神薬理学会　2009
高次脳機能における心臓型脂肪酸結合蛋白質 (H-FABP)の役割.

本橋慧樹, 橋本茜, 塩田倫史, 近藤尚武, 大和田祐二, 福永浩司

第128年会日本薬学会年会　2008
心臓型脂肪酸結合タンパク質（H-FABP/FABP3）の中枢神経系における機能解析

本橋慧樹, 齋野幸子, 北中のり子, 安達泰弘, 徳田信子, 澤田知夫, 福永浩司, 近藤尚武, 大和田祐二

第113回日本解剖学会総会・全国学術集会　2008
中枢神経系における脂肪酸の機能制御因子としての心臓型脂肪酸結合タンパク質 (H-FABP)

本橋慧樹, 橋本茜, 塩田倫史, 近藤尚武, 大和田祐二, 福永浩司

第１８回霧島神経薬理フォーラム　2007
心臓型脂肪酸結合タンパク質（H-FABP）の中枢神経系における機能解析

本橋慧樹, 北中のり子, 安達泰弘, 徳田信子, 澤田知夫, 福永浩司, 大和田祐二

日本解剖学会第62回中国・四国支部学術集会　2007
高次脳機能における心臓型脂肪酸結合蛋白質 (H-FABP)の役割

本橋慧樹, 橋本茜, 塩田倫史, 近藤尚武, 大和田祐二, 福永浩司

第60回日本薬理学会西南部会　2007

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Research Projects 47

Elucidation of the mechanism of lipid mediator modulation and exacerbation of inflammatory bowel disease due to impaired fatty acid transport

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Dokkyo Medical University

2025/04/01 - 2028/03/31
Molecular Mechanism of Regulation of Immune System Cellular Functions by Lipid Nutrition during Development

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2022/04/01 - 2025/03/31
脳発達期の脂肪酸栄養が発達障害の発症増悪に与える影響

山本由似, 大和田祐二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北医科薬科大学

2022/04/01 - 2025/03/31
Molecular mechanism underlying immune cell responses regulated by lipid intake during development

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2022/04/01 - 2025/03/31
Significance of lipid nutrition in the pathological mechanisms of neurodegenerative and psychiatric diseases

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Institution: Tohoku University

2020/10/27 - 2025/03/31
Effect of lipo-quality of adipocytes on tumor growth and invasion

Owada Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2022/06/30 - 2024/03/31

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There is an urgent need to elucidate the mechanisms by which excessive lipid intake, a factor in metabolic syndrome and other lifestyle-related diseases, acts on various diseases, including cancer. In this study, we examined the effects of changes in lipid composition and lipid metabolism in the cancer microenvironment, which are altered by dietary intake, on the biological activity of cancer. The results indicated that linoleic acid and linolenic acid, essential fatty acids, play an important role in cell death of pancreatic cancer cells, and that oleic acid and fatty acid binding protein (FABP7), an intracellular carrier of oleic acid, may be involved in the distant metastatic potential of skin cancer.
胎児期からの脂肪酸摂取バランスが炎症性腸疾患の寛解と再燃に与える影響

徳田信子, 大和田祐二, 入澤篤志, 山本由似

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 獨協医科大学

2020/04/01 - 2023/03/31

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我々が着目してきた、脂肪酸シャペロンである脂肪酸結合タンパク質(fatty acid binding protein, FABP)について、免疫細胞や免疫応答、細胞の増殖制御に関する知見を重ねている。FABPを欠損した動物は、胎児期からの脂肪酸摂取バランスに異常を持つ動物モデルとして捉えている。我々がすでにリンパ節や脾臓の樹状細胞への存在を報告してきたFABP5（表皮型FABP）については、制御性T細胞の活性化の制御や、NK細胞の成熟の制御に関与することを明らかにした。また、リンパ節や脾臓の特定の線維芽細胞に発現することを見い出し報告してきたFABP7（脳型FABP）については、肝マクロファージにも発現し、FABP7の炎症への関与を明らかにしてきた。FAPB7は肝線維化過程に役割を果たしていると考えられ、その機能について解析を続けている。これらのFABPは、炎症細胞だけではなく、種々の腫瘍細胞の増殖にも関与しており、疾患の治療への応用も期待されている。 FABP7は、炎症が惹起された際、腸管やリンパ節で増殖する線維芽細胞に発現することをすでに確認し報告してきた。FABP7は、特に、T細胞が多く集積している部分の線維芽細胞に発現する。また、炎症前にはFABP7が全く発現していない部位の線維芽細胞に、その発現が見られるようになる。現在、デキストラン硫酸ナトリウムで誘発した腸炎モデルを作成し、このモデルにおけるT細胞の反応について解析している。動物モデルから得られた結果については、実臨床への応用を検討している。
Exploration of cancer cell microenvironment network focusing on the adipocytes

OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2020/07/30 - 2022/03/31

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It has been shown that nutritional imbalance, especially unbalanced lipid intake, is closely related to lifestyle-related diseases such as diabetes and hypertension. Obesity, in particular, is considered a factor that influences the risk of carcinogenesis such as breast cancer and the prognosis of cancer, but the mechanisms involved are still unclear. In this study, we investigated the effects of the lipid microenvironment within and around tumors on proliferation and invasion. As a result, it became clear that the lipid environment dramatically changes the activation status of immune cells around tumors including melanoma, and eventually influence the tumor progression.
Molecular basis of neural cell response to the nutritional intake of fatty acids during development

OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Although higher brain functions and neurological diseases have been linked to nutritional intake, the molecular basis of the effects of lipids on the nervous system has remained unclear. In this application, we examined whether changes in lipid metabolism in nervous system cells (neurons and glial cells) are related to the regulation of genetic information (epigenetic modification) and neural plasticity. The results revealed that changes in intracellular lipid metabolism and energy production affect the stress response of glial cells and the plasticity of neurons.
Elucidation of epigenome regulation mechanism by fatty acid binding protein

yamamoto yui

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku Medical and Pharmaceutical University

2019/04/01 - 2022/03/31

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It has been suggested that lipid homeostasis changes in developmental brain are associated with abnormal neuroplasticity after growth. In this study, we examined the relationship between abnormal lipid metabolism and changes in neuroplasticity in inhibitory interneurons and astrocytes that are particularly vulnerable to environmental changes during development. We mainly revealed that fatty acid binding protein (FABP) in the cortical inhibitory interneurons is involved in the expression of cognitive and emotional behaviors through regulation of neurite outgrowth, and that FABP in astrocyte is important in the control of lipid metabolism and it is also involved in the neuronal plasticity control through epigenetic regulation of genetic information. These results are expected to contribute to the research and development of mental illness and health medicine.
ω６長鎖脂肪酸を介した神経炎症制御に対して脂肪酸結合蛋白質が果たす役割

大和田祐二, PAN YIJUN

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特別研究員奨励費

Category: 特別研究員奨励費

Institution: 東北大学

2018/11/09 - 2020/03/31

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野生型および脂肪酸結合タンパク質（FABP)の遺伝子欠損マウスに対して、通常食とアラキドン酸などの多価不飽和脂肪酸含量を調整した餌（脂質コントロール食餌）で、長期間（2－3か月）飼育しながら、摂食量、体重、血清データ等を集積し、既報の解析モデルとして使用できることを確認した。その後、各種行動解析（行動量、オープンフィールド、Y迷路、高架十字迷路、水迷路等）を施行した。その結果、脂質コントロール食投与後の行動変化について、野生型と変異マウス間で優位な差異が認められた。行動解析後に、マウスから各臓器(空腸、回腸、肝臓、心臓、腎臓、脳、脊髄等）をサンプリングし、脂質成分分析用の凍結した状態で保存するとともに、形態学的解析用に固定標本の準備を進めている。
Exploring the new regulatory mechanism underlying hypothalamic capillary dynamics

Owada Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2018/06/29 - 2020/03/31

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aWe analyzed the possibility that the distribution of capillaries in the hypothalamus might change in a mouse high fat diet administration model. As a result, it was found that long-term administration of a high-fat diet changes the distribution of capillaries that do not have a blood-brain barrier. We are currently analyzing the nutrition and other external stimulus responses of glial cells and nerve cells around these capillaries. In addition, we examined the relationship between mitochondrial function and nutrient responsiveness in hypothalamic neurons. Analysis of mice lacking Ndufs4, which is a major constituent protein of the mitochondrial electron transport system, revealed that hypothalamic hormone (GnRH) secretion, which regulates pituitary gonadotropin production, was decreased in hypothalamic neurons and abnormal myelination of myelinated nerves was observed. Was found to be recognized.
Control of obesity and inflammatory bowel disease by polyunsaturated fatty acid adjusted diet

Nobuko Tokuda

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

2017/04/01 - 2020/03/31

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Intake of n-3 fatty acid deficient diet and deficiency of FABP7 (brain-type fatty acid binding protein), which has high affinity for n-3 fatty acids, may affect weight gain, peripheral immune cell number and differentiation. FABP7 deficiency suppressed food intake and obesity when a high-fat diet was consumed. FABP7 has also been shown to play a role in regulating inflammation and protecting cell death. Another polyunsaturated fatty acid regulator has also been shown to control the exacerbation of inflammatory bowel disease.
Significance of lipid metabolism in glial cell function: association with psychiatiric diseases

Owada Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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In this study, we aimed to clarify the molecular basis how the cellular lipid environment affects the function of neural cells including neurons and glia. In addition, we also explored whether alteration of brain lipid metabolism is associated with the normal or pathological brain functions. We mainly revealed that fatty acid binding protein (FABP) in the cortical neurons is involved in the expression of behaviors through its epigenetic regulation of neurotransmitter synthesis, and that FABP in glia is important in the control of glial lipid metabolism and it is also involved in the glial proliferation and neuronal plasticity control through epigenetic regulation of lipid metabolism. These results are expected to contribute to research and development in the fields of psychiatry and health sciences.
Fatty acid binding protein in the anterior cingulate cortex modulates GABAergic system

YAMAMOTO Yui, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku Medical and Pharmaceutical University

2016/04/01 - 2019/03/31

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In this study, we show that FABP3 is strongly expressed in the GABAergic inhibitory interneurons of the mouse anterior cingulate cortex (ACC). Interestingly, FABP3 KO mice show an increase in the expression of the gene encoding the GABA-synthesizing enzyme glutamic acid decarboxylase 67 (Gad67) in the ACC. In the ACC of FABP3 KO mice, Gad67 promoter methylation and the binding of methyl-CpG binding protein 2 (MeCP2) and histone deacetylase 1 (HDAC1) to the Gad67 promoter are significantly decreased compared with those in WT mice.
Role of glia in hypothalamic nutrient sensing

Yasumoto Yuki, OWADA YUJI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

Category: Grant-in-Aid for Research Activity Start-up

Institution: Tohoku University

2016/08/26 - 2018/03/31

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In this study, we established OPC specific dysfunction mouse, performed morphological analysis by 3D electron microscopy and examined the role of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC. We performed a phenotypic analysis of diet-induced FABP7 knockout (KO) obese mice and of FABP7 KO mice treated with a single leptin injection. In mice fed a high-fat diet, weight gain and food intake were lower in FABP7 KO mice than in wild type (WT) mice. FABP7 KO mice also had lower food intake and weight gain after a single injection of leptin, and we consistently confirmed that the number of pSTAT3+ cells in the ARC indicated that the leptin-induced activation of neurons was significantly more frequent in FABP7 KO mice than in WT mice. These results indicate that in hypothalamic astrocytes, FABP7 might be involved in sensing neuronal leptin via glia-mediated mechanisms and plays a pivotal role in controlling systemic energy homeostasis.
Novel mechanism how hypothalamus senses the lipid of the blood.

Owda Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2016/04/01 - 2018/03/31

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The hypothalamus is involved in the regulation of food intake and energy homeostasis. However, the molecular mechanisms involved in these activities remain largely unknown. In this study, we examined in detail the localization of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC. Immunohistochemistry revealed that FABP7+ cells are NG2+ or GFAP+ in the ARC. In mice fed a high-fat diet, weight gain and food intake were lower in FABP7 KO mice than in wild-type (WT) mice. FABP7 KO mice also had lower food intake and weight gain after a single injection of leptin, and we consistently confirmed that the number of pSTAT3+ cells in the ARC indicated that the leptin-induced activation of neurons was significantly more frequent in FABP7 KO mice than in WT mice.
Genome epidemiological study on sleep and mental health

Kadotani Hiroshi, Yoshikawa Takeo, Owada Yuji, Gerstner Jason R., Perron Isaac J., Riedy Samantha M., Van Dongen Hans P. A., Galante Raymond J., Dickinson Kaitlin, Yin Jerry C. P., Pack Allan I., Frank Marcos G.

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Shiga University of Medical Science

2014/04/01 - 2018/03/31

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The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes. We found from our genome epidemiological study that the missense mutation FABP7.T61M is associated with fragmented sleep. This phenotype was recapitulated in mice and fruit-flies bearing similar mutations. This was a result from an international collaborating study.
Effects of fatty acids on the obese patients suffered from inflammatory bowel disease and development of examination of feces

TOKUDA Nobuko, TSUNEOKA Hidehiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Yamaguchi University

2014/04/01 - 2017/03/31

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Fibroblastic reticular cells (FRCs) produce collagen-rich reticular fibers in immune organs. We have shown FRCs express fatty acid binding protein 7 (FABP7), a chaperon which has a high affinity to n-3 polyunsaturated fatty acids. Similar fibroblasts were seen in inflamed intestine. Mice were infected on the skin of the flank with simplex virus type 1 (HSV-1) and the responses in the primary draining brachial LN (bLN) were analyzed. After HSV infection, expansion and proliferation of bLN FRCs increased and Fabp7 genes were highly upregulated in FRCs. Expression of FABP7 mRNA in FRCs after HSV infection were significantly upregulated. However, any deficiency was not defined and expansion of FRCs was unaffected compared with wild-type mice. In diet-induced fat mice, FABP7 might affect the increasing fibroblasts. FABP7 and some chaperons may be involved in fibroblast homeostasis, possibly by modulating lipid metabolism in fibroblasts at the inflammation including high fat state.
Fatty acid binding protein regulates higher brain function via lipid metabolism regulation

YAMAMOTO Yui, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Yamaguchi University

2014/04/01 - 2016/03/31

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In this study, we examined the role of fatty asid binding protein 3 (FABP3) in the regulation of GABA synthesis and neurotransmission, mainly by using FABP3 gene ablated mice. The following results have been so far obtained: 1. In ACC of FABP3 KO mice, GAD67 promoter methylation and binding of MeCP2 and HDAC1 to GAD67 promoter were significantly decreased compared with wild-type mice. 2. To determine whether FABP3 directly regulates synaptic plasticity in the ACC, we recorded the amplitude and frequency of miniature IPSCs (mIPSCs) in ACC neurons. the mIPSC frequency was significantly increased in FABP3 KO mice compared with wild-type mice. On the other hand, the mIPSC amplitude was unchanged, suggesting that the loss of FABP3 produces alterations in inhibitory synaptic transmission. These findings suggest that DNA hypomethylation and the associated chromatin remodeling underlie the elevation of GAD67 in ACC and the abnormal behaviors and excitatory/inhibitory balance of FABP3 KO mice.
Molecular basis and physiological function of cellular lipid homeostasis in the brain and immune stromal cells

Owada Yuji, YOSHIKAWA Takeo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

2012/04/01 - 2016/03/31

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In this study, we revealed for the first time that alteration of lipid homeostasis in the glial cells affects their response to the external stimuli such as growth factors. We showed that intracellular lipid binding protein, FABP7, regulates the membrane lipid raft function in astrocytes through the caveolin gene expression. We also showed that glial FABP7 is involved in the control of excitatory synaptic neurotransmission in the medial frontal cortex, and possible associated with the human psychiatric diseases including schizophrenia.
Possiblity of fatty acid binding protein as a diagnostic and therapeutic target in glioma

OWADA Yuji, SUZUKI Michiyasu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Yamaguchi University

2013/04/01 - 2015/03/31

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In this study, we tried to develop the sensitive diagnostic tool for glioblastoma focusing on fatty acid binding protein (FABP7), and examined the possibility as a regulator of glioma proliferation. We firstly established the sensitive ELISA assay system to detect FABP7 and measured its concentration in the cerebro-spinal fluid (CSF) samples from the patient suffering from glioma. As a result, FABP7 concentration in the CSF was markedly elevated in the glioblastoma patients compared with healthy controls. In the pathological examination in glioma samples, levels of FABP7 expression were significantly correlated with their malignancy grade. Furthermore, suppression of FABP7 expression in glioma stem cell lines by siRNA transfection resulted in the decreased proliferation.
Effects of lipids on the function of thymic epithelial cells

ADACHI Yasuhiro, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: University of Occupational and Environmental Health, Japan

2012/04/01 - 2015/03/31

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In the present study, we examined the effect of fatty acids and function of fatty acid-binding protein 5 (FABP5) in thymopoiesis, morphology and proliferation/differentiation of thymic epithelial cells through the comparison of wild-type (WT) and FABP5-knock out (KO) mice. We found that long chain-polyunsaturated fatty acids (LC-PUFAs) and rerinoic acid (RA) promotes proliferation of cultured thymic epithelial cells via FABP5 rather than the specific function of thymic epithelial cells which regulates differentiation of thymocytes.
Role of fatty acid binding proteins for regulation of neural plasticity

YAMAMOTO YUI, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

Category: Grant-in-Aid for Research Activity Start-up

Institution: Yamaguchi University

2012/08/31 - 2014/03/31

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In this study, we examined the role of fatty asid binding proteins (FABPs) in the regulation of cellular signaling transduction, mainly by using FABP gene ablated mice. The following results have been so far obtained: 1. brain-type FABP (FABP7) and epidermal-type FABP (FABP5) are differentially expressed in oligodendrocyte lineage cells and regulate their proliferation and/or differentiation(Sharifi et al., Cell and Tissue Res 2013). 2. heart-type FABP (FABP3) gene ablation in mice resulted in altered cognitive and emotional behaviors with the decrease of PUFA uptake into the brain. Basal GABA release was significantly increased in the contex of FABP3 gene ablated mice, while glutamate release was significantly decreased compared with wild-type mice.
Influence of maternal intake of n-3 fatty acid on fatty acid transport of fetal blood brain barrier

TOKUDA NOBUKO, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Yamaguchi University

2011 - 2013

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Epidemiological studies suggest that maternal dietary poor intake of n-3 and some fatty acids may trigger certain mental disorders of fetus. However, the molecular basis of their actions is still unknown. Our findings show that fatty acid binding protein 3 (FABP3) controls fatty acid trafficking in mouse placenta and the transport is important for fetal development. FABP3 also regulates cognitive function and anxiety behaviors. In mouse brain, FABP5 and FABP7 are differentially expressed in oligodendrocyte lineage cells and regulate their proliferation and/or differentiation.
Application of focal brain cooling for intractable epilepsy

SUZUKI Michiyasu, OWADA Yuji, FUJII Masami, NOMURA Sadahiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Yamaguchi University

2010 - 2012

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Safeness of focal brain cooling (FBC) for intractable epilepsy was verified. A rat epilepsy model was treated by the FBC. The optimal temperature to interrupt seizure without deteriorating neuronal function was 15 ℃. The FBC was applied at epilepsy surgery in human. Increased levels of glutamate and lactate reduced at 15 ℃. The FBC effectively inhibit neuronal excitotoxicity and anaerobic metabolism. Newly developed cooling device was successfully applied to cats and monkeys.
Epidermal fatty acid binding protein (EFAP/FABP5) expression is associated with differential transcytosis of M cells in C57BL/6 mice Peyer's patch

SUZUKI Ryoji, ABE Hiroshi, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Akita University

2010 - 2012

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Epidermal fatty acid binding protein (EFAP/FABP5) expression in M cell in C57BL/6 mice Peyer's patch drastically increased during intestinal flora conversion. Terminal web accumulation ofEFABP in M cell might be driven by EFABP-galectin4 complex synthesis. Both in vivo and in vitro study showed that aboveEFABP expression conversion andEFABP-galectin4 complex were associated with intestinal antigen transcytosis.
Mechanism by which fatty acid binding proteins regulate the cellular signal transduction

OWADA Yuji, TOKUDA Nobuko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Yamaguchi University

2009 - 2011

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In this study, we examined the role of fatty acid binding proteins in the regulation of cellular signal transduction, mainly by using FABP-deficient mice. The following results have been so far obtained :(1) epidermal-type FABP(FABP5) is involved in the early differentiation process of mouse keratinocytes though the regulation of linoleic acid metabolism(Ogawa et al., J Invest Dermatol, 2011).(2) brain-type FABP(FABP7) is involed in the proliferation of astrocytes through the regulation of omega-3 polyunsaturated fatty acid metabolism(Sharifi et al., Histochem Cell Biol, 2011).
Identification of Epileptogenic Focus by Employing Softcomputing and Establishment of Minimally Invasive and Definitive Surgery

YAMAKAWA Takeshi, SUZUKI Michiyasu, YAMAKAWA Toshitaka, AOU Shuji, ISHIZUKA Satoru, HORIO Keiichi, FUJII Masami, NOMURA Sadahiro, OWADA Yuji, GRIGORIEVICH Zimin lev, TOKIWA Tatsuji, INOUE Takao, MARUTA Yuichi, FUJIOKA Hiroshi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Specially Promoted Research

Category: Grant-in-Aid for Specially Promoted Research

Institution: Kyushu Institute of Technology

2008 - 2011

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The patients comprising about 0. 2% of the total population, in the country or overseas, are insensitive to antiepileptic drug and left to the surgical operation. The operation often causes a residual disability because of its accuracy of epileptogenic focus estimation and extirpation with some margin. Our project was dedicated to seeking for the accurate estimation method of the focus and the surgical procedure including the flash freeze-thaw technology and the laser ablation technology.
Analysis of functional significance of lipids in receptors for vision, hearing and olfaction by way of functional analysis of fatty acid binding proteins

SAINO Sachiko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku Bunka Gakuen University

2008 - 2010

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In the retina of normal adult mice, B-FABP was mainly localized in the cone photoreceptor cells, H-FABP in some populations of amacrine/bipolar/horizontal interneurons, and E-FABP in ganglion cells, suggesting the discrete functional involvement of FABPs and their ligands, FAs in the photoreception and photo-transmission. In addition, A-FABP-like immunoreactivity was located in resident microglia of normal retinae. In damaged retinae following photic injury, E-FABP was intensely localized in invasive macrophages, allowing discrete identification of the resident microglia and invasive macrophages by A- and E-FABP immunoreactivity, respectively. In the inner ear of normal adult mice, H (heart- type) -FABP was localized in inner and outer pillar cells and outer phalangeal cells, while B (brain-type)-FABP was localized in border cells and cells of Hensen, and fibrocytes in the spiral limbus and spiral prominence. However, no hair cells expressed any species of FABPs. Althoug the FABP species and/or their ligands, FAs, is suggested to play important roles in the regulation of the hearing function, mutant mice with deletion of the gene for either H- or B-FABP did not show any impairment of the hearing ability. In addition to the two sensory organs, E-FABP was expressed/localized in most, if not all, populations of the dendritic cells in the subepithelial domes, follicles and interfollicular regions of Peyer's patches and presumptive macrophages in their germinal centers, and all M cells in the follicle-associated epithelium of mouse intestine. The immunoreactivity in both of the cell populations makes it easy to recognize the accumulation of DCs in the subepithelial domes in close proximity to the base of M cells, which is essential for luminal antigens to be transported to Peyer's patches. E-FABP may play some important roles in the mucosal immune reaction through Peyer's patches and associated structures.
Analysis of B-FABP as an immunoregulatory factor by modulating omega-3 polyunsaturated fatty acid metabolism

TOKUDA Nobuko, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Yamaguchi University

2008 - 2010

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The present study was undertaken to examine the detailed distribution and the function of brain-type fatty acid binding protein (B-FABP/FABP7), a strong binder of omega-3 fatty acids, in mouse peripheral immune organs and immune cells. B-FABP was localized to the fibroblastic reticular cells, which construct the stromal reticula in the T cell areas of the peripheral lymph nodes and spleen. In B-FABP knockout (KO) mice, the percentage of CD4^+ cells in the organs was significantly increased compared with that in wild-type mice. In the liver, B-FABP was exclusively localized in Kupffer cells. Their phagocytic activity and accumulation to injured portion were significantly decreased in KO mice.
A role of fatty acid binding protein as a regulator of cellular functions

OWADA Yuji, TOKUDA Nobuko, ADACHI Yasuhiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Yamaguchi University

2007 - 2008
アストロサイトの分裂制御因子としてのB-FABP:グリオーマ治療応用への可能性

澤田知夫, 大和田祐二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 山口大学

2007 - 2008

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脂肪酸結合蛋白質(FABP)は長鎖脂肪酸と結合、可溶化し、細胞膜や細胞小器官や核に運搬する。本研究では、FABPファミリーのうちアストロサイトや一部のグリオーマ細胞に豊富に存在するB-FABPが、細胞の増殖・遊走などの形質に関与しているかどうか検討するために、野生型およびB-FABP-KO(B-KO)のC57BL/6マウスから得た初代培養アストロサイトを用いてB-FABP欠損の影響を解析した。野生型マウスから得た培養アストロサイトで、培養10日後までのB-FABP発現が確認できた。B-KOアストロサイトの増殖、遊走、接着を解析したところ、B-KOアストロサイトではBrdU取込みが野生型より低く、培養皿との接着能も野生型より低かった。また、遊走能のっいては差が検出できなかった。次に申請者らは、B-FABPがどのような経路で細胞の増殖、接着に影響を与えるのかについて検討した。洲Aマイクロアレイ解析によりB-KOアストロサイトでのconnexin43発現の低下が示唆されたが、蛋白量の差は検出できなかった。脂肪酸が関連する代謝・シグナル伝達系の分子については、DNAマイクロアレイ解析でApoEの発現低下が示されたが、蛋白量としての低下は確認できなかった。転写因子PPARα,β,γ、およびCD36とLox-2について、DNAマイクロアレイ解析も蛋白質の解析も共に、それらがほとんど初代培養アストロサイトに発現しないことを示した。 B-FABPとNFkBシグナル伝達系との関連性をウェスタンブロットにより検討した結果、NFkB活性を制御するIkBαのリン酸化がB-KOアストロサイトで低下しており、B-FABP欠損によるアストロサイト分裂能の減少がNFKBの活性低下によりもたらされている可能性が示唆された。
Analysis of Novel Cellular Functions of Fatty Acid Binding Proteins

KONDO Hisatake, OWADA Yuji, SAKAGAMI Hiroyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2006 - 2007

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Mutant mice for epidermal (E)-type and brain (B)-type fatty acid binding proteins (FABPs) were successfully generated as the first attempts in the world by us and they were fully analyzed throughout the project. The mutants for B-FABP exhibited enhanced anxiety and increased fear memory in the behavioral examination, while they decreased the content of docosahezaenoic acid (DHA) in the brain only at neonatal period without any histological changes in the brain at adult or neonate stages. The B-FABP mutants also showed decreased prepulse inhibition whose deficits are a biological marker for schizophrenia. All the data suggest a novel and crucial role of B-FABP in the pathology of schizophrenia. The mutants for E-FABP exhibited a lower mortality rate in the peritonitis by infection of Salmonella as compared with the wild counterpart. By in vitro analysis, dendritic cells isolated from the mutant spleen showed enhanced production of IL-12p70 in response to appropriate stimuli and higher levels of phosphorylated forms of p38 mitogen-activated protein kinase and IkBa after LPS stimulation as compared with the wild. These results suggest that the lower mortality rate in the peritonitis of the mutants was due to the possible role of E-FABP as a negative regulator of IL-12 production in the dendritic cells.
Function analysis of fatty acid binding protein in the immune cells

0WADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

2005 - 2006

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In order to clarify the physiological function of fatty acid binding proteins in the immune cells, we examined the phenotype of FABP knockout mice, and obtained the following results during this research period: 1) Epidermal-type fatty acid binding protein (E-FABP) deficient mast cells showed the decreased production of TNFa and IL-6, proinflammatory cytokines, in response to LPS. Furthermore, E-FABP deficient mice showed an increased mortality in the septic peritonitis model in vivo (under submission). 2) E-FABP deficient dendritic cells (DC) showed the marked increase of IL-12 production after LPS stimulation., and the phosphorylation of P38MAPK and IkappaBK was much higher in the E-FABP deficient DC compared with wild-type (Kitanaka et al., BBRC, 2006). 3) Expression of adopocyte-type FABP (A-FABP) was markedly enhanced in the lymphocytes after dexamethasone treatment, which are known to induce the apoptosis in the lymphocytes (abdelwahab et al., Mol Cell Biochem, 2007). These data strongly suggest that FABPs expressed in the various immune cells serve as a modulator of various immune reactions including cytokine production and apoptosis.
Differentiation disturbance in keratinocytes lacking the epidermal fatty acid binding protein gene (E-FABP) which is overexpressed in psoriatic lesions.

HASHIMOTO Akira, OKUYAMA Ryuhei, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2005 - 2006

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Fatty acid binding proteins (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate intracytoplasmic sites. Among FABP consisting of at least 13 isoforms, keratinocytes only express epidermal-type FABP (E-FABP) which is overexpressed in actively proliferating states like psoriasis and healing wounds. We analyzed functions of E-FABP using E-FABP null keratinocytes. Our examinations revealed decreased amount of fatty acids, especially of linoleic acid, in the E-FABP null epidermis. Although no difference in the growth of the E-FABP null keratinocytes with that of wild cells, the null keratinocytes showed decrease of induction of differentiation specific proteins (keratin 1 and involcrin). Linoleic acid did not modulate the keratinocyte differentiation directly, but linoleic acid derivatives, hydroxyoctadecadienoic acid (HODE), induced the differentiation specific proteins. Moreover, HODE activated NF-kB signal pathway which promoted keratinocyte differentiation. The activity of NF-kB pathway was decreased in the E-FABP null keratinocytes, which supported the idea that the decreased linoleic acid connects disturbed differentiation via the derivatives of linoleic acid. On the other hand, peroxisome proliferator activated receptor (PPAR) pathway, which had been reported as main target of E-FABP, did not show any difference in the E-FABP null keratinocytes. From our results, E-FABP affects NF-kB pathway through fatty acid metabolism, which may connect E-FABP overexpression with pathomechanism in psoriasis because NF-kB plays important roles in cell survival and differentiation.
Functional analysis of fatty acid binding proteins in immune and neural tissues.

KONDO Hisatake, OWADA Yuji, SAKAGAMI Hiroyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2002 - 2003

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Among fatty acid binding proteins (FABPs), the localization of brain(B)-and epidermal (E)-FABPs were examined in details in varous organs/tissues of mice, and gene knockout mice for the two FABPs were generated and their phenotypes were analysed in neuro-immune systems. While B-FABP was localized in the ventricular germinal zone and radial glial cells at prenatal stages and confined to the astrocytes in postnatal brain, E-FABP was localized in neurons and glia at the perinatal stage and confined to astrocytes in postnatal brain. While B-FABP was localized only in hepatic Kupffer cells, E-FABP was localized in splenic dendritic cells, peritoneal and alveolar macrophages, and thymic epithelical cells of adult mice. With the new advantage of E-FABP as a specific marker for the dendritc cells, the phagocytosis of lipopolysaccharide-induced apoptotic splenocytes in situ by the dendritic cells was first revealed. The basal transepidermal water loss of homozygous mice for E-FABP was lower than that of the wild mice. When the water permeability barrier of skin was disrupted by aceton application, recovery in transepidermal water loss was delayed, although no marked differences ware detected in ultrastructure and lipid contents of epidermis. Dendritic cells isolated from E-FABP-homozygous mice showed a marked decrease of IL-12 secretion. B-FABP-homozygous mice showed deterioration of learnining, memory anxiety.
Functional analysis of fatty acid binding proteins in the brain

OWADA Yuji, KONDOH Hisatake

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2002 - 2003

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It was shown that fatty acids, especially docosahexiaenoic acid and arachidonic acid, are important in the verious brain functions, including learning and memory functions. Brain type-fatty acid binding protein (B--FABP) belongs to a family of intracellular lipid binding proteins. B-FABP exhibits a higher binding affinity to docosahexaenoic acid (DNA) whose effect on learning and memory function has been documented, and it is localized in the ventricular germinal cells in embryonic brain and astroglia in adult brain of rodents. The present study generated mice harboring a null mutation in the B-FABP gene and the phenotype analysis of the gene-knockout mice exhibited the impaired learning, and memory function. and the decreased content of DNA in their brain without detection of any histological changes in the brain. Furthermore, the response of NMDA receptor-mediated current to DNA in isolated hippocampal neurons from the B-FABP mutant mice was significantly decreased in comparison with that of wild mice. These data indicate that B-FABP in the glia is intimately involved in the well-known effect of DHA on learning and memory.
神経疾患バイオセンサーとしての脂肪酸結合タンパクの可能性追及

近藤尚武, 大和田祐二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2002 - 2003

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本申請では、組織および細胞に比較的高い発現特異性を有する脂肪酸結合タンパク分子ファミリーに着目し、測定が簡便でしかも鋭敏な疾患マーカーとしてFABPが機能するか否かを、マウス疾患モデルを用いた基礎的解析から検証した。現在までに以下のような結果を得ている。まず測定法としては、微量なタンパクを検出するのにすぐれた方法であるサンドイッチELISA法の条件検討を行い、5種類のFABP(脳型B-、上皮型E-、心臓型H-、肝臓型L-および脂肪細胞型A-FABP)のピコグラムレベルのタンパクを血清および臓器から定量的に検出する方法を確立した。さらに、応用の第1段階として、マウス肺にLPSを経気管的に投与したARDS(急性呼吸不全症候群)モデルを作成し、血中および肺胞洗浄液中のFABP量を定量したところ、L-FABPの発現がLPS投与後早期に血中レベルで上昇することを突き止めた。また同時に、L-FABPが肺胞マクロファージに発現することも、形態学的解析によって証明した。これまでに鋭敏なマーカーの開発が望まれていたARDSの発症余地や重傷度の指標としてL-FABPが有用であることを示した。以上の結果は、現在欧文誌に投稿中である。
海馬シナプス可塑性調節および神経細胞死における脂肪酸結合蛋白の機能追及

近藤尚武, 梅宮正志, 大和田裕二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽的研究

Category: 萌芽的研究

Institution: 東北大学

2000 - 2001

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(研究目的) 脂肪酸結合蛋白(FABP)は、AAを始めとする長鎖脂肪酸に高い親和性を有する脂肪酸の細胞内担体てあり、脂肪酸の細胞膜移動や細胞内動態に深く関与することが知られている。脂肪酸の細胞輸送分子の神経系細胞における生理機能を明らかにするために、我々が樹立したFABP遺伝子欠損マウスを用いて以下の2つの研究項目について検討する。 (研究経過と結果) FABPと神経可塑性について我々がこれまでに施行したFABPに関する解析で、神経系には上皮型(E-)、脳型(B-)、心臓型(H-)FABPの3種のFABPアイソフォームが発現していることが知られている。本研究期間に樹立が終了したE-、B-FABPノックアウトマウス神経系に対する形態学的解析からは、両者とも明らかな異常を示さないことが判明した一方、一部の神経細胞では心臓型FABPの代償制の発現増強が観察された(Mol Cell Biochem, J Invest Dermatol in press)。現在これらのマウスに対して行動学的な解析を鋭意施行中である。また他のアイソフォームによる代償性発現を排除するために神経系に発現するE-、B-、H-FABPのダブルノックアウトの作成および解析を進めている。 FABPと神経細胞死の関連について我々はこれまでに明らかにした、舌下神経軸索損傷モデルの舌下神経核運動ニューロンにおける上皮型FABPの発現の意義を検討するためにE-FABPノックアウトマウスにおける舌下神経切断後の表現型を運動ニューロンにおいて検討した。切断後の舌下神経の形態学的解析からは、野生型とノックアウトマウスの間に明らかな相違は観察できなかった。現在ダブルノックアウトマウスあるいは、培養神経細胞における神経ストレス反応の解析を思考中である。
Molecular and Cell Biological Analysis of lipid kinases and phosphatases involved in phosphoinosilide signaling

KONDO Hisatake, SAITO Sachiko, OWADA Yuji

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).

Category: Grant-in-Aid for Scientific Research (B).

Institution: Tohoku University

1999 - 2000

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In an in situ hybridization histochemical study on the localization of mRNA for SHIP2, SH2-domain containing inositol 5-phosphatase SHIP isozyme in the brain of developing and mature rats. It was detected in the ventricular germinal zone at embryonic stages. As the postnatal development proceeded, the expression was evident in cells of the white matters, presumptive oligodendrocytes, without significant expression in neurons throughout the development. In another study on the localization of PLD mRNAs, the expression of PLD1 mRNA was detected in presumptive oligodendrocytes, while PLD2 mRNA was expressed mainly in presumptive astrocytes. In addition, the gene expression for PLDs were detected in neuroepithelial cells of the ventricular/ependymal zones and the gene for PLD2 was expressed transiently in early postnatal gray matters, presumptive neurons. In the other study the localization of mRNAs for 10 isoforms of protein kinase C (PKC) in the rat brain was studied at embryonic and postnatal stages. In the embryonic brain, the gene expression was positive only for PKCε, μ, λ, ζ with the former three more evident ; the expression for PKCμ, I in the ventricular germinal zone and that for PKCε, ζ, λ in the mantle zone. In the postnatal brain, the expression for PKCζ, η, θ was detected differentially in a few circumscribed loci such as the thalamus, habenula, septum and cerebellar granule cells, whereas that for the other isoforms was seen widely in various loci of the gray matter with different intensity. The expression in the cerebellar external granule cell layer was positive only for PKCβ, μ, λ with that for PKCβ confined to its inner zone. There is a general tendency for all PKC isoforms that the expression levels reach at peaks in carly postnatal brain and decreases more or less in adult specimens.
Molecular and Celluler Biological Analysis of the functional Significance of Phosphoinositide Metabolism

KONDO Hisatake, OWADA Yuji, GOTO Kaoru, SAITO Sachiko, KANOH Hideo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

1999 - 2000

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In a study (Kondo, Owada, SainoSaito) on the localization of mRNA for SHIP2, SH2-domain containing inositol 5-phosphatase SHIP isozyme in the brain of developing and mature rats, it was detected in the ventricular germinal zone at embryonic stages. As the postnatal development proceeded, the expression was evident in cells of the white matters, presumptive of oligodendrocytes, without significant expression in neurons throughout the development. In another study (Kondo, Owada, SainoSaito) on the localization of PLD mRNAs, the expression of PLD1mRNA was detected in presumptive oligodendrocytes, while PLD2 mRNA was expressed mainly in presumptive astrocytes, although the gene for PLD2 was expressed transiently in early postnatal gray matters, presumptive neurons. The transgenic mice for PI4kinases was generated using a DBH-promoter and the examination on the effect in membrane transport was performed using the Golgi fraction of chromaffin cells (SainoSaito, Ross), although the results are not confirmative. The gene knockout mice for PAP2A was generated but the phenotype of knockout mice was not evident (Kanoh, Kondo). The gene knockout mice for FABPs was successfully done and their phenotypes have been analyzed biochemically and morphologically (Kondo, Owada, Spener). The cDNA cloning of PLAI was succeeded and the localization of its mRNA was examined in the adult brain of monkey, resulting in the intense expression in the cerebellar granule and Purkinje cells (Glomset, Goto, Kondo). The localization of PIPKI and PKPKII was examined in the rat brain and in vitro cells (Irvine, Kondo) and PIPKI was found to directly interact with ADP-ribosylation factor I and be responsible for PIP synthesis in the Golgi compartment using our PI4K cDNA and cell biological methodologies. Intimate discussion was made through E-mail about the functional significance of DGK, PAP and some other PI-related molecules with Merida and Perrozzi.
脂肪酸結合蛋白の神経細胞死抑制機能の検討

大和田祐二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業奨励研究(A)

Category: 奨励研究(A)

Institution: 東北大学

1998 - 1999

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アラキドン酸などの長鎖脂肪酸は、神経細胞の種々の生理機能に関与することが既に知られている。本研究期間で我々は、長鎖脂肪酸の細胞内キャリアーである脂肪酸結合蛋白(FABP)の神経系細胞の分化および細胞死に関する生体機能を明確にするために以下の実験を施行した。 <実験> 1)皮膚型FABP遺伝子欠損マウスを作製し神経系の発達異常の有無を主に形態学的手法を用いて検討した。 2)皮膚型FABPの遺伝子・蛋白レベルの発現誘導が証明されている舌下神経軸索切断モデルを用いて、ノックアウトマウスと野生型マウスの比較から、舌下神経核運動ニューロンの形態学的解析を加えた。 3)脳型FABP遺伝子欠損マウスの作製に着手した。 <結果と進行状況> 1)皮膚型FABP遺伝子欠損マウスは正常に発育し、神経系の形成異常などはこれまでのころと観察されていない。 2)舌下神経切断後7日における解析では、ノックアウトマウスと野生型マウスの間に有意な運動ニューロンの光顕的変化は見られない。 3)脳型FABP遺伝子欠損マウスの作製は、現在ES細胞の選択を終了し、キメラマウスの作製を行っている。
脂肪酸結合蛋白を介した神経系細胞の細胞周期制御脳腫瘍治療応用への可能性の追求

近藤尚武, 吉本高志, 大和田祐二

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽的研究

Category: 萌芽的研究

Institution: 東北大学

1998 - 1999

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アラキドン酸やドコサヘキサエン酸などの長鎖脂肪酸は、神経系細胞の分裂・分化制御因子として知られている。本研究期間で我々は、長鎖脂肪酸の細胞内キャリアーである脂肪酸結合蛋白(FABP)の神経系細胞の分裂および形態形成に関する生体機能を明確にするために以下の実験を施行した。 <実験> 1)皮膚型FABP遺伝子欠損マウスを作製し神経系の発達異常の有無を、主に形態学的手法を用いて検討した。 2)脳型FABP遺伝子欠損マウスの作製に着手した。 <結果と進行状況> 1)皮膚型FABP遺伝子欠損マウスは正常に発育し、神経系の形成異常などはこれまでのところ観察されていない。 2)皮膚型FABP遺伝子欠損マウスでは、一部の神経細胞において、心臓型FABPの代償的な蛋白発現誘導が観察された。 3)脳型FABP遺伝子欠損マウスの作製は、現在ES細胞の選択を終了し、キメラマウスの作製を行っている。 <総括> 遺伝子欠損マウスの解析結果は、FABPの複数のアイソフォームが神経系細胞の分裂・分化プロセスにおいて互いに代償的機能を果たす事実を示唆している。
新たに同定した肝特異的ホスホイノシチド3-キナーゼ〜肝癌発生と進展への関与〜

竹内丙午, 遠藤公人, 大和田祐二, 海野倫明, 鈴木正徳

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

1998 - 1998

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われわれがラットにおいてクローニングした新しいホスホイノシチド3-キナーゼ(PI3K-IIγ)の発現が,臓器特異的に肝に集中しており,また,PI3Kは細胞増殖に関与することが知られていた.そこで,肝細胞癌を研究対象に,PI3K-IIγの癌化機構への関わりを検討する研究を立案し,平成10年4月より実験的研究を開始した. まず,われわれの持つラットPI3K-IIγのcDNA塩基配列よりプライマーを設計し,ヒト型PI3K-IIγのcDNAクローニングに着手した.プライマーは,nest-PCR施行のため4種類作成し,LA-Taq酵素を用いて,ヒトPI3K-IIγの翻訳領域のうち,約1000塩基対のcDNAクローニングに成功した.このcDNAのシークエンス分析を行うとともに,これをプローブとしてヒトcDNAライブラリーをスクリーニングし,非翻訳領域を含めた全長のcDNAの同定に成功した. 続いて,ヒトPI3K-IIγのN-およびC-末端側から,ほかのPI3Kアイソザイムと類似性低い部分のアミノ酸配列,各々20アミノ酸を選び,そのcDNAを発現ベクターに組み込み大腸菌で発現させた.この際に,発現させるペプチドのN末側にGSTを付加するような発現ベクターを用い,ペプチド回収にはGST結合カラムを用いた。このペプチドをウサギに免疫するよう保存した。この作業と平行して,ヒト肝細胞株(HepG2,HT-17など計5種)を培養し,それらのRNAを抽出してNorthern Blot法によるPI3K-IIγ遺伝子発現の解析を行った。はじめtotal RNAを用いて解析したところ発現が認められなかったため,poly(A)+RNAの精製まで行っている。
The regulation mechanism of lipid kinase in the signal transduction

KONDO Hisatake, SPENER F., CANTLEY L.C., GLOMSET J.A., HUNT D.M., GOTO Kaoru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for international Scientific Research

Category: Grant-in-Aid for international Scientific Research

Institution: Tohoku University

1997 - 1998

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A cDNA encoded a 462-amino acid protein, which showed CDP-diacylglycerol synthase (CDS) activity was cloned for the first time as the vertebrate enzyme molecule from rat brain cDNA library. The deduced molecular mass of this CDS was 53 kDa, and putative primary structure included several possible membrane-spanning regions. This enzyme molecule preferred 1-stearoyl- 2-arachidonoyl phosphatidate as a substrate and its activity was strongly inhibited by phosphatidylinositol (PtdIns) 4,5-bisphosphate. The molecule was mainly localized in close association with the membrane of the endoplasmic reticulum of over-expressed in vitro cells. The intense mRNA expression of CDS was localized in the cerebellar Purkinje cells, pineal body, and the inner segment of photoreceptor cells, and postmitotic spermatocytes and spermatids of testis of mature rats. This finding is closely similar to that of arachidonoyl-diacylglycerol kinase (DGK) and in this regard we discussed with Dr.J.A.Glomset who first identified the DGK and attempted to examine the colocalization of the two molecules by immunohistochemistry by Drs.K.Goto. A novel DGK was identified by cDNA cloning from human brain and retina cDNA library and termed DGKtheta in co-operation with Dr.W.J.van Blitterswijk. DGKtheta was composed of 951 amino acids and contained three cysteine-rich domain, a proline- and glycine-rich domain with a putative SH3 domain-binding site and a pleckstrin homology domain with an overlapping Ras-associating domain. In adult rat brain high expression was detected in the cerebellar cortex and hippocampus. The cloning and characterization of a novel class II phosphoinositide 3-kinase was succeeded from the cDNA library of regenerating rat liver. This enzyme molecule composed of1505 amino acids contained a C2 domain and displayed a restricted substrate specificity for PtdIns and PtdIns 4-P and, thus termed PI3K-IIgamma. This molecule was localized in the juxtanuclear Golgi region in the over-expressed in vitro cells. The mRNA expression was confined to the liver throughout the development and its expression increased during liver regeneration after partial hepatectomy. Further molecular characterization is under way in co-operation with Dr.L.C.Cantley. By in situ hybridization histochemistry a dramatic increase in expression of Akt was detected in affected hypoglossal nucleus after 2-7 days following axotomy of the hypoglossal nerve. Such an increase in the gene expression after axotomy was observed in a similar time course for PI3 kinase and skin type-fatty acid binding protein (FABP), suggesting a functional relation between PI-signal and FABP.Thus the gene knockout for s-FABP is under way in co-operation with Dr.F.Spener. The gene expression localization of phospholipase D in the brain is also under way in cooperation with Dr.Y.Nozawa. The chromosome mapping of the genome for PtdIns 4-kinase was attempted in cooperation with Dr.D.M.Hunt and started. However, in the course of experiment we unfortunately found that it has already done by another foreign research group and thus gave up this attempt.
Molecular and Cell Biological Analysis of Lipid Kinases in Relation to Signaling and Vesicle Traffic.

KONDO Hisatake, GOTO Kaoru, OWADA Yuji, SAKAGAMI Hiroyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

1997 - 1998

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The cloning and characterization of a novel class II phosphoinositide (PI) 3-kinase was succeeded from the cDNA library of regenerating rat liver. This enzyme molecule composed of 1505 amino acids contained a C2 domain and displayed a restricted substrate specificity for PtdIns and PtdIns 4-P and, thus termed PI3K-IIgamma. This molecule was localized in the juxtanuclear Golgi region in the over-expressed in vitro cells. The mRNA expression was confined to the liver throughout the development and its expression increased during liver regeneration after partial hepatectomy. The gene expression for a subtype of phosphatidate (PA) phosphatase termed Dri42 was confined to the ventricular germinal zone of embryonic brain. PAP catalyses a dephosphorylation of PA to produce diacylglycerol (DG), an reverse process of phosphorylation by DG kinase whose molecular identification has been intensively performed by us. The localization of mRNAs for synaptojanin, inositol 5-phosphatase, in the brain was also revelaed by in situ hybridization histochemistry. Synaptojanin 1 mRNA was expressed in almost all neurons of the brain throughout developing and mature stages while synaptojanin 2 mRNA was first detected in neurons on early postnatal stages and the expression was evident in the white matters presumptive oligodendrocytes as the postnatal development proceeded. All these findings on dephosphorylation were instructive for understanding the significance of phosphorylation by lipid kinases. The gene expression localization of CDP-DG synthase and phosphatidylinositol synthase, both of which are involved in the two sequential PI-metabolic processes, was analyzed and some discrepant expression patterns were found spatio-temporally in developing and mature brain. The gene expression localization of phospholipase D in the brain is also under way by in situ hybridization histochemistry.

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Teaching Experience 3

発生学　山口大学
組織学　東北大学、山口大学
解剖学　東北大学、山口大学