Details of the Researcher

PHOTO

Motoko Maekawa
Section
Graduate School of Medicine
Job title
Associate Professor
Degree

  • 博士（医学）（東北大学）

Research History 8

  • 2022/01 - Present
    Tohoku University

  • 2021/06 - 2021/12
    Tohoku University

  • 2019/11 - 2021/05
    国立研究開発法人理化学研究所　CBSキャリア形成推進プログラム　上級研究員

  • 2019/04 - 2019/10
    国立研究開発法人理化学研究所　CBS キャリア形成推進プログラム　研究員

  • 2018/04 - 2019/03
    国立研究開発法人理化学研究所　CBS 分子精神遺伝　研究員

  • 2015/04 - 2018/03
    国立研究開発法人理化学研究所　BSI 分子精神科学　研究員

  • 2008/04 - 2015/03
    RIKEN

  • 2006/04 - 2008/03
    国立精神・神経センター 神経研究所・微細構造研究部　流動研究員

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Research Interests 46

  • C3H/He マウス

  • C3H/HeNマウス

  • 脂肪酸

  • アミノ酸

  • C57BL/6 マウス

  • C57BL/6Nマウス

  • PPI

  • ビタミン

  • 22q11.2欠乏症候群

  • オリゴデンドロサイト

  • ARMS

  • GABA

  • 環境要因

  • B6マウス

  • 栄養

  • 環境因子

  • 母子間伝達物質

  • 神経発達

  • 母乳

  • C3マウス

  • 必須脂肪酸

  • DNAChip

  • カナビノイド受容体

  • シグナルパスウェイ

  • 神経分化

  • 統合失調症

  • 神経新生

  • 不飽和脂肪酸

  • Pax6変異ヘテロラット

  • プレパルス抑制(PPI)

  • 発達

  • 死後脳

  • 気分障害

  • 遺伝子解析

  • FABP3

  • FABP7

  • 多価不飽和脂肪酸

  • FABP5

  • 情動記憶

  • Fyn チロシンキナーゼ

  • 恐怖条件付け

  • 記憶の消去

  • 扁桃体

  • NMDA受容体

  • 海馬

  • 文脈的記憶

Research Areas 1

  • Life sciences / Molecular biology /

Papers 75

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin β-cluster genes in the developing brain. International-journal

    Shabeesh Balan, Yoshimi Iwayama, Tetsuo Ohnishi, Mikiko Fukuda, Atsuko Shirai, Ayumi Yamada, Sara Weirich, Maren Kirstin Schuhmacher, Kalarickal Vijayan Dileep, Toshihiro Endo, Yasuko Hisano, Kaoru Kotoshiba, Tomoko Toyota, Takeshi Otowa, Hitoshi Kuwabara, Mamoru Tochigi, Akiko Watanabe, Hisako Ohba, Motoko Maekawa, Manabu Toyoshima, Tsukasa Sasaki, Kazuhiko Nakamura, Masatsugu Tsujii, Hideo Matsuzaki, Kam Y J Zhang, Albert Jeltsch, Yoichi Shinkai, Takeo Yoshikawa

    Molecular psychiatry　26　(12)　7550-7559　2021/07/15

    DOI： 10.1038/s41380-021-01199-7 　

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    Recent evidence has documented the potential roles of histone-modifying enzymes in autism-spectrum disorder (ASD). Aberrant histone H3 lysine 9 (H3K9) dimethylation resulting from genetic variants in histone methyltransferases is known for neurodevelopmental and behavioral anomalies. However, a systematic examination of H3K9 methylation dynamics in ASD is lacking. Here we resequenced nine genes for histone methyltransferases and demethylases involved in H3K9 methylation in individuals with ASD and healthy controls using targeted next-generation sequencing. We identified a novel rare variant (A211S) in the SUV39H2, which was predicted to be deleterious. The variant showed strongly reduced histone methyltransferase activity in vitro. In silico analysis showed that the variant destabilizes the hydrophobic core and allosterically affects the enzyme activity. The Suv39h2-KO mice displayed hyperactivity and reduced behavioral flexibility in learning the tasks that required complex behavioral adaptation, which is relevant for ASD. The Suv39h2 deficit evoked an elevated expression of a subset of protocadherin β (Pcdhb) cluster genes in the embryonic brain, which is attributable to the loss of H3K9 trimethylation (me3) at the gene promoters. Reduced H3K9me3 persisted in the cerebellum of Suv39h2-deficient mice to an adult stage. Congruently, reduced expression of SUV39H1 and SUV39H2 in the postmortem brain samples of ASD individuals was observed, underscoring the role of H3K9me3 deficiency in ASD etiology. The present study provides direct evidence for the role of SUV39H2 in ASD and suggests a molecular cascade of SUV39H2 dysfunction leading to H3K9me3 deficiency followed by an untimely, elevated expression of Pcdhb cluster genes during early neurodevelopment.

  6. Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia. International-journal

    Tetsuo Ohnishi, Yuji Kiyama, Fumiko Arima-Yoshida, Mitsutaka Kadota, Tomoe Ichikawa, Kazuyuki Yamada, Akiko Watanabe, Hisako Ohba, Kaori Tanaka, Akihiro Nakaya, Yasue Horiuchi, Yoshimi Iwayama, Manabu Toyoshima, Itone Ogawa, Chie Shimamoto-Mitsuyama, Motoko Maekawa, Shabeesh Balan, Makoto Arai, Mitsuhiro Miyashita, Kazuya Toriumi, Yayoi Nozaki, Rumi Kurokawa, Kazuhiro Suzuki, Akane Yoshikawa, Tomoko Toyota, Toshihiko Hosoya, Hiroyuki Okuno, Haruhiko Bito, Masanari Itokawa, Shigehiro Kuraku, Toshiya Manabe, Takeo Yoshikawa

    EMBO molecular medicine　13　(4)　e12574　2021/04/09

    DOI： 10.15252/emmm.202012574 　

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    Genomic defects with large effect size can help elucidate unknown pathologic architecture of mental disorders. We previously reported on a patient with schizophrenia and a balanced translocation between chromosomes 4 and 13 and found that the breakpoint within chromosome 4 is located near the LDB2 gene. We show here that Ldb2 knockout (KO) mice displayed multiple deficits relevant to mental disorders. In particular, Ldb2 KO mice exhibited deficits in the fear-conditioning paradigm. Analysis of the amygdala suggested that dysregulation of synaptic activities controlled by the immediate early gene Arc is involved in the phenotypes. We show that LDB2 forms protein complexes with known transcription factors. Consistently, ChIP-seq analyses indicated that LDB2 binds to > 10,000 genomic sites in human neurospheres. We found that many of those sites, including the promoter region of ARC, are occupied by EGR transcription factors. Our previous study showed an association of the EGR family genes with schizophrenia. Collectively, the findings suggest that dysregulation in the gene expression controlled by the LDB2-EGR axis underlies a pathogenesis of subset of mental disorders.

  7. Role of an Atypical Cadherin Gene, Cdh23 in Prepulse Inhibition, and Implication of CDH23 in Schizophrenia. International-journal

    Shabeesh Balan, Tetsuo Ohnishi, Akiko Watanabe, Hisako Ohba, Yoshimi Iwayama, Manabu Toyoshima, Tomonori Hara, Yasuko Hisano, Yuki Miyasaka, Tomoko Toyota, Chie Shimamoto-Mitsuyama, Motoko Maekawa, Shusuke Numata, Tetsuro Ohmori, Tomomi Shimogori, Yoshiaki Kikkawa, Takeshi Hayashi, Takeo Yoshikawa

    Schizophrenia bulletin　47　(4)　1190-1200　2021/02/17

    DOI： 10.1093/schbul/sbab007 　

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    We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the previously reported QTLs with increased marker density. The highest logarithm of odds score (26.66) peaked at a synonymous coding and splice-site variant, c.753G>A (rs257098870), in the Cdh23 gene on chromosome 10; the c.753G (C3H) allele showed a PPI-lowering effect. Bayesian multiple QTL mapping also supported the same variant with a posterior probability of 1. Thus, we engineered the c.753G (C3H) allele into the B6 genetic background, which led to dampened PPI. We also revealed an e-QTL (expression QTL) effect imparted by the c.753G>A variant for the Cdh23 expression in the brain. In a human study, a homologous variant (c.753G>A; rs769896655) in CDH23 showed a nominally significant enrichment in individuals with schizophrenia. We also identified multiple potentially deleterious CDH23 variants in individuals with schizophrenia. Collectively, the present study reveals a PPI-regulating Cdh23 variant and a possible contribution of CDH23 to schizophrenia susceptibility.

  8. Lipid Pathology of the Corpus Callosum in Schizophrenia and the Potential Role of Abnormal Gene Regulatory Networks with Reduced Microglial Marker Expression. International-journal

    Chie Shimamoto-Mitsuyama, Akihiro Nakaya, Kayoko Esaki, Shabeesh Balan, Yoshimi Iwayama, Tetsuo Ohnishi, Motoko Maekawa, Tomoko Toyota, Brian Dean, Takeo Yoshikawa

    Cerebral cortex (New York, N.Y. : 1991)　31　(1)　448-462　2021/01/01

    DOI： 10.1093/cercor/bhaa236 　

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    Structural changes in the corpus callosum have been reported in schizophrenia; however, the underlying molecular mechanism remains unclear. As the corpus callosum is high in lipid content, we analyzed the lipid contents of the corpora callosa from 15 patients with schizophrenia and 15 age- and sex-matched controls using liquid chromatography coupled to tandem mass spectrometry and identified lipid combinations associated with schizophrenia. Real-time quantitative polymerase chain reaction analyses using extended samples (schizophrenia, n = 95; control, n = 91) showed low expression levels of lipid metabolism-related genes and their potential upstream transcription factors in schizophrenia. Subsequent pathway analysis identified a gene regulatory network where nuclear factor of activated T cells 2 (NFATC2) is placed most upstream. We also observed low gene expression levels of microglial markers, inflammatory cytokines, and colony-stimulating factor 1 receptor (CSF1R), which is known to regulate the density of microglia, in the corpus callosum in schizophrenia. The interactions between CSF1R and several genes in the presently identified gene network originating from NFATC2 have been reported. Collectively, this study provides evidence regarding lipid abnormalities in the corpora callosa of patients with schizophrenia and proposes the potential role of impaired "NFATC2-relevant gene network-microglial axis" as its underlying mechanism.

  9. Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia. International-journal

    Yuina Wada, Motoko Maekawa, Tetsuo Ohnishi, Shabeesh Balan, Shigeru Matsuoka, Kazuya Iwamoto, Yoshimi Iwayama, Hisako Ohba, Akiko Watanabe, Yasuko Hisano, Yayoi Nozaki, Tomoko Toyota, Tomomi Shimogori, Masanari Itokawa, Tetsuyuki Kobayashi, Takeo Yoshikawa

    EBioMedicine　62　103130-103130　2020/12

    DOI： 10.1016/j.ebiom.2020.103130 　

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    BACKGROUND: The pathophysiology of schizophrenia, a major psychiatric disorder, remains elusive. In this study, the role of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor (RXR) families, belonging to the ligand-activated nuclear receptor superfamily, in schizophrenia, was analyzed. METHODS: The PPAR/RXR family genes were screened by exploiting molecular inversion probe (MIP)-based targeted next-generation sequencing (NGS) using the samples of 1,200 Japanese patients with schizophrenia. The results were compared with the whole-genome sequencing databases of the Japanese cohort (ToMMo) and the gnomAD. To reveal the relationship between PPAR/RXR dysfunction and schizophrenia, Ppara KO mice and fenofibrate (a clinically used PPARα agonist)-administered mice were assessed by performing behavioral, histological, and RNA-seq analyses. FINDINGS: Our findings indicate that c.209-2delA, His117Gln, Arg141Cys, and Arg226Trp of the PPARA gene are risk variants for schizophrenia. The c.209-2delA variant generated a premature termination codon. The three missense variants significantly decreased the activity of PPARα as a transcription factor in vitro. The Ppara KO mice exhibited schizophrenia-relevant phenotypes, including behavioral deficits and impaired synaptogenesis in the cerebral cortex. Oral administration of fenofibrate alleviated spine pathology induced by phencyclidine, an N-methyl-d-aspartate (NMDA) receptor antagonist. Furthermore, pre-treatment with fenofibrate suppressed the sensitivity of mice to another NMDA receptor antagonist, MK-801. RNA-seq analysis revealed that PPARα regulates the expression of synaptogenesis signaling pathway-related genes. INTERPRETATION: The findings of this study indicate that the mechanisms underlying schizophrenia pathogenesis involve PPARα-regulated transcriptional machinery and modulation of synapse physiology. Hence, PPARα can serve as a novel therapeutic target for schizophrenia.

  10. 核内受容体PPARαと統合失調症病態メカニズムの関連

    和田 唯奈, 大西 哲生, 小林 哲幸, 吉川 武男, 前川 素子

    日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集　50回・42回・4回　191-191　2020/08

    Publisher: 日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会

  11. 脳梁における脂質代謝異常と統合失調症

    島本 知英, Balan Shabeesh, 岩山 佳美, 江崎 加代子, 大西 哲生, 前川 素子, Dean Brian, 吉川 武男

    日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集　50回・42回・4回　191-191　2020/08

    Publisher: 日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会

  12. VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction. International-journal

    Noriyoshi Usui, Keiko Iwata, Taishi Miyachi, Shu Takagai, Keisuke Wakusawa, Takahiro Nara, Kenji J Tsuchiya, Kaori Matsumoto, Daisuke Kurita, Yosuke Kameno, Tomoyasu Wakuda, Kiyokazu Takebayashi, Yasuhide Iwata, Toru Fujioka, Takaharu Hirai, Manabu Toyoshima, Tetsuo Ohnishi, Tomoko Toyota, Motoko Maekawa, Takeo Yoshikawa, Masato Maekawa, Kazuhiko Nakamura, Masatsugu Tsujii, Toshiro Sugiyama, Norio Mori, Hideo Matsuzaki

    EBioMedicine　58　102917-102917　2020/08

    DOI： 10.1016/j.ebiom.2020.102917 　

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    BACKGROUND: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation. METHODS: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses. FINDINGS: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children. INTERPRETATION: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology. FUNDING: This study was supported mainly by MEXT, Japan.

  13. Evaluation of the role of fatty acid-binding protein 7 in controlling schizophrenia-relevant phenotypes using newly established knockout mice. International-journal Peer-reviewed

    Chie Shimamoto-Mitsuyama, Tetsuo Ohnishi, Shabeesh Balan, Hisako Ohba, Akiko Watanabe, Motoko Maekawa, Yasuko Hisano, Yoshimi Iwayama, Yuji Owada, Takeo Yoshikawa

    Schizophrenia research　217　52-59　2020/03

    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.

  14. A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder. International-journal

    Motoko Maekawa, Tetsuo Ohnishi, Manabu Toyoshima, Chie Shimamoto-Mitsuyama, Kei Hamazaki, Shabeesh Balan, Yuina Wada, Kayoko Esaki, Shu Takagai, Kenji J Tsuchiya, Kazuhiko Nakamura, Yasuhide Iwata, Takahiro Nara, Yoshimi Iwayama, Tomoko Toyota, Yayoi Nozaki, Hisako Ohba, Akiko Watanabe, Yasuko Hisano, Shigeru Matsuoka, Masatsugu Tsujii, Norio Mori, Hideo Matsuzaki, Takeo Yoshikawa

    Brain communications　2　(2)　fcaa145　2020

    DOI： 10.1093/braincomms/fcaa145 　

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    Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behaviour. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n = 123) and typically developing children (n = 92) at 4-12 years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of fatty acid binding protein 4 (FABP4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4-6 years old: n = 21 for autism spectrum disorder and n = 26 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder-like behavioural phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an 'adipo-brain axis' may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker.

  15. Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology. International-journal Peer-reviewed

    Masayuki Ide, Tetsuo Ohnishi, Manabu Toyoshima, Shabeesh Balan, Motoko Maekawa, Chie Shimamoto-Mitsuyama, Yoshimi Iwayama, Hisako Ohba, Akiko Watanabe, Takashi Ishii, Norihiro Shibuya, Yuka Kimura, Yasuko Hisano, Yui Murata, Tomonori Hara, Momo Morikawa, Kenji Hashimoto, Yayoi Nozaki, Tomoko Toyota, Yuina Wada, Yosuke Tanaka, Tadafumi Kato, Akinori Nishi, Shigeyoshi Fujisawa, Hideyuki Okano, Masanari Itokawa, Nobutaka Hirokawa, Yasuto Kunii, Akiyoshi Kakita, Hirooki Yabe, Kazuya Iwamoto, Kohji Meno, Takuya Katagiri, Brian Dean, Kazuhiko Uchida, Hideo Kimura, Takeo Yoshikawa

    EMBO molecular medicine　11　(12)　e10695　2019/12

    DOI： 10.15252/emmm.201910695 　

    ISSN： 1757-4676

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    Mice with the C3H background show greater behavioral propensity for schizophrenia, including lower prepulse inhibition (PPI), than C57BL/6 (B6) mice. To characterize as-yet-unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H2 S)/polysulfide-producing enzyme, and greater sulfide deposition in C3H than B6 mice. Mpst-deficient mice exhibited improved PPI with reduced storage sulfide levels, while Mpst-transgenic (Tg) mice showed deteriorated PPI, suggesting that "sulfide stress" may be linked to PPI impairment. Analysis of human samples demonstrated that the H2 S/polysulfides production system is upregulated in schizophrenia. Mechanistically, the Mpst-Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H2 S/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory/oxidative insults in early brain development result in upregulated H2 S/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H2 S/polysulfides production.

  16. 統合失調症の病態メカニズムにおける核内受容体PPARαの役割

    和田 唯奈, 大西 哲生, 小林 哲幸, 吉川 武男, 前川 素子

    日本脳科学会プログラム・抄録集　46回　29-29　2019/11

    Publisher: 日本脳科学会

  17. 統合失調症の病態メカニズムにおける核内受容体PPARαの役割

    和田 唯奈, 大西 哲生, 小林 哲幸, 吉川 武男, 前川 素子

    日本脳科学会プログラム・抄録集　46回　29-29　2019/11

    Publisher: 日本脳科学会

  18. Investigation of betaine as a novel psychotherapeutic for schizophrenia. International-journal Peer-reviewed

    Tetsuo Ohnishi, Shabeesh Balan, Manabu Toyoshima, Motoko Maekawa, Hisako Ohba, Akiko Watanabe, Yoshimi Iwayama, Yuko Fujita, Yunfei Tan, Yasuko Hisano, Chie Shimamoto-Mitsuyama, Yayoi Nozaki, Kayoko Esaki, Atsuko Nagaoka, Junya Matsumoto, Mizuki Hino, Nobuko Mataga, Akiko Hayashi-Takagi, Kenji Hashimoto, Yasuto Kunii, Akiyoshi Kakita, Hirooki Yabe, Takeo Yoshikawa

    EBioMedicine　45　432-446　2019/07

    DOI： 10.1016/j.ebiom.2019.05.062 　

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    BACKGROUND: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. METHODS: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. FINDINGS: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. INTERPRETATION: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).

  19. Thiosulfate promotes hair growth in mouse model. International-journal Peer-reviewed

    Motoko Maekawa, Tetsuo Ohnishi, Shabeesh Balan, Yasuko Hisano, Yayoi Nozaki, Hisako Ohba, Manabu Toyoshima, Chie Shimamoto, Chinatsu Tabata, Yuina Wada, Takeo Yoshikawa

    Bioscience, biotechnology, and biochemistry　83　(1)　114-122　2019/01

    DOI： 10.1080/09168451.2018.1518705 　

    ISSN： 0916-8451

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    The present study describes the hair growth-promoting effects of sodium thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth in the "telogen model", suggesting that it stimulates telogen hair follicles to reenter the anagen phase of hair growth. In the same model, STS potentiated hair growth in an additive manner with minoxidil (MXD), a drug used for the treatment of androgenic alopecia. Furthermore, in the "anagen model", STS promoted hair growth, probably by promoting hair follicle proliferation. Since STS elevated the skin surface temperature, its hair growth-promoting activity may be partly due to vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous mediator, H2S, which has vasorelaxation and anti-inflammatory/anti-oxidative stress activities. Therefore, STS and/or provisionally its metabolite, H2S, may aid the hair growth process. Collectively, these results suggest that salts of thiosulfate may represent a novel and beneficial remedy for hair loss.

  20. Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation. International-journal Peer-reviewed

    Akiko Matsuura, Tamaki Ishima, Yuko Fujita, Yoshimi Iwayama, Shunsuke Hasegawa, Ryouka Kawahara-Miki, Motoko Maekawa, Manabu Toyoshima, Yusuke Ushida, Hiroyuki Suganuma, Satoshi Kida, Takeo Yoshikawa, Masaomi Iyo, Kenji Hashimoto

    Scientific reports　8　(1)　2158-2158　2018/02/01

    DOI： 10.1038/s41598-018-20538-3 　

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    Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions. Particularly, MIA increased the expression of suppressor of fermentation-induced loss of stress resistance protein 1 (Sfi1) mRNA in the PFC and hippocampus of adult offspring, and dietary intake of GF prevented the expression of Sfi1 mRNA in these regions. Interestingly, we found altered expression of SFI1 in the postmortem brains and SFI1 mRNA in hair follicle cells from patients with schizophrenia compared with controls. Overall, these data suggest that centrosome-related genes may play a role in the onset of psychosis in offspring after MIA. Therefore, dietary intake of GF-rich vegetables in high-risk psychosis subjects may prevent the transition to psychosis in young adulthood.

  21. Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes Peer-reviewed

    M. Maekawa, A. Watanabe, Y. Iwayama, T. Kimura, K. Hamazaki, S. Balan, H. Ohba, Y. Hisano, Y. Nozaki, T. Ohnishi, M. Toyoshima, C. Shimamoto, K. Iwamoto, M. Bundo, N. Osumi, E. Takahashi, A. Takashima, T. Yoshikawa

    TRANSLATIONAL PSYCHIATRY　7　2017/09

    DOI： 10.1038/tp.2017.182 　

    ISSN： 2158-3188

  22. Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia. International-journal Peer-reviewed

    Shabeesh Balan, Kazuo Yamada, Yoshimi Iwayama, Takanori Hashimoto, Tomoko Toyota, Chie Shimamoto, Motoko Maekawa, Shu Takagai, Tomoyasu Wakuda, Yosuke Kameno, Daisuke Kurita, Kohei Yamada, Mitsuru Kikuchi, Tasuku Hashimoto, Nobuhisa Kanahara, Takeo Yoshikawa

    Schizophrenia research　185　33-40　2017/07

    DOI： 10.1016/j.schres.2017.01.003 　

    ISSN： 0920-9964

    eISSN： 1573-2509

  23. Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice. International-journal Peer-reviewed

    Naoko Morimura, Hiroki Yasuda, Kazuhiko Yamaguchi, Kei-Ichi Katayama, Minoru Hatayama, Naoko H Tomioka, Maya Odagawa, Akiko Kamiya, Yoshimi Iwayama, Motoko Maekawa, Kazuhiko Nakamura, Hideo Matsuzaki, Masatsugu Tsujii, Kazuyuki Yamada, Takeo Yoshikawa, Jun Aruga

    Nature communications　8　15800-15800　2017/06/12

    DOI： 10.1038/ncomms15800 　

    ISSN： 2041-1723

  24. Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder Peer-reviewed

    K. Hamazaki, M. Maekawa, T. Toyota, B. Dean, T. Hamazaki, T. Yoshikawa

    EUROPEAN PSYCHIATRY　39　51-56　2017/01

    DOI： 10.1016/j.eurpsy.2016.05.007 　

    ISSN： 0924-9338

    eISSN： 1778-3585

  25. Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations. International-journal Peer-reviewed

    Xiaoxi Liu, Takafumi Shimada, Takeshi Otowa, Yu-Yu Wu, Yoshiya Kawamura, Mamoru Tochigi, Yasuhide Iwata, Tadashi Umekage, Tomoko Toyota, Motoko Maekawa, Yoshimi Iwayama, Katsuaki Suzuki, Chihiro Kakiuchi, Hitoshi Kuwabara, Yukiko Kano, Hisami Nishida, Toshiro Sugiyama, Nobumasa Kato, Chia-Hsiang Chen, Norio Mori, Kazuo Yamada, Takeo Yoshikawa, Kiyoto Kasai, Katsushi Tokunaga, Tsukasa Sasaki, Susan Shur-Fen Gau

    Autism research : official journal of the International Society for Autism Research　9　(3)　340-9　2016/03

    DOI： 10.1002/aur.1536 　

    ISSN： 1939-3792

    eISSN： 1939-3806

  26. Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study. International-journal Peer-reviewed

    Kei Hamazaki, Motoko Maekawa, Tomoko Toyota, Yoshimi Iwayama, Brian Dean, Tomohito Hamazaki, Takeo Yoshikawa

    Schizophrenia research　171　(1-3)　225-32　2016/03

    DOI： 10.1016/j.schres.2016.01.014 　

    ISSN： 0920-9964

    eISSN： 1573-2509

  27. Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. International-journal 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

  28. 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

  29. Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism. International-journal 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　16239-16239　2015/11/09

    DOI： 10.1038/srep16239 　

    ISSN： 2045-2322

  30. 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.

  31. Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder. International-journal Peer-reviewed

    Kei Hamazaki, Motoko Maekawa, Tomoko Toyota, Brian Dean, Tomohito Hamazaki, Takeo Yoshikawa

    Psychiatry research　227　(2-3)　353-9　2015/06/30

    DOI： 10.1016/j.psychres.2015.01.004 　

    ISSN： 0165-1781

  32. Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. International-journal 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)　780-94　2015/05

    DOI： 10.1002/glia.22784 　

    ISSN： 0894-1491

    eISSN： 1098-1136

  33. Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies. International-journal 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　2015/04/15

    DOI： 10.1093/hmg/ddv011 　

    ISSN： 0964-6906

    eISSN： 1460-2083

  34. Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia Peer-reviewed

    Shabeesh Balan, Yoshimi Iwayama, Kazuo Yamada, Tomoko Toyota, Tetsuo Ohnishi, Manabu Toyoshima, Chie Shimamoto, Masayuki Ide, Yasuhide Iwata, Katsuaki Suzuki, Mitsuru Kikuchi, Tasuku Hashimoto, Nobuhisa Kanahara, Takeo Yoshikawa, Motoko Maekawa

    JOURNAL OF NEURAL TRANSMISSION　122　(3)　477-485　2015/03

    DOI： 10.1007/s00702-014-1269-0 　

    ISSN： 0300-9564

    eISSN： 1435-1463

  35. 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

  36. Ceramide galactosyltransferase expression is regulated positively by Nkx2.2 and negatively by OLIG2 Peer-reviewed

    Kyohei Okahara, Yasuhiko Kizuka, Shinobu Kitazume, Fumi Ota, Kazuki Nakajima, Yoshio Hirabayashi, Motoko Maekawa, Takeo Yoshikawa, Naoyuki Taniguchi

    GLYCOBIOLOGY　24　(10)　926-934　2014/10

    DOI： 10.1093/glycob/cwu042 　

    ISSN： 0959-6658

    eISSN： 1460-2423

  37. Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects Peer-reviewed

    Shabeesh Balan, Yoshimi Iwayama, Motoko Maekawa, Tomoko Toyota, Tetsuo Ohnishi, Manabu Toyoshima, Chie Shimamoto, Kayoko Esaki, Kazuo Yamada, Yasuhide Iwata, Katsuaki Suzuki, Masayuki Ide, Motonori Ota, Satoshi Fukuchi, Masatsugu Tsujii, Norio Mori, Yoichi Shinkai, Takeo Yoshikawa

    MOLECULAR AUTISM　5　(1)　49　2014/10

    DOI： 10.1186/2040-2392-5-49 　

    ISSN： 2040-2392

  38. 22q11.2 deletion carriers and schizophrenia-associated novel variants Peer-reviewed

    S. Balan, Y. Iwayama, T. Toyota, M. Toyoshima, M. Maekawa, T. Yoshikawa

    BRITISH JOURNAL OF PSYCHIATRY　204　(5)　398-399　2014/05

    DOI： 10.1192/bjp.bp.113.138420 　

    ISSN： 0007-1250

    eISSN： 1472-1465

  39. Possibility of Polyunsaturated Fatty Acids for the Prevention and Treatment of Neuropsychiatric Illnesses Peer-reviewed

    Michio Hashimoto, Motoko Maekawa, Masanori Katakura, Kei Hamazaki, Yutaka Matsuoka

    JOURNAL OF PHARMACOLOGICAL SCIENCES　124　(3)　294-300　2014/03

    DOI： 10.1254/jphs.13R14CP 　

    ISSN： 1347-8613

    eISSN： 1347-8648

  40. Lack of association of EGR2 variants with bipolar disorder in Japanese population Peer-reviewed

    Shabeesh Balan, Kazuo Yamada, Yoshimi Iwayama, Tomoko Toyota, Tetsuo Ohnishi, Motoko Maekawa, Manabu Toyoshima, Yasuhide Iwata, Katsuald Suzuki, Mitsuru Kikuchi, Hiroshi Ujike, Toshiya Inada, Hiroshi Kunugi, Norio Ozaki, Nakao Iwata, Shinichiro Nanko, Tadafumi Kato, Takeo Yoshikawa

    GENE　526　(2)　246-250　2013/09

    DOI： 10.1016/j.gene.2013.05.055 　

    ISSN： 0378-1119

    eISSN： 1879-0038

  41. Population-Specific Haplotype Association of the Postsynaptic Density Gene DLG4 with Schizophrenia, in Family-Based Association Studies Peer-reviewed

    Shabeesh Balan, Kazuo Yamada, Eiji Hattori, Yoshimi Iwayama, Tomoko Toyota, Tetsuo Ohnishi, Motoko Maekawa, Manabu Toyoshima, Yasuhide Iwata, Katsuaki Suzuki, Mitsuru Kikuchi, Takeo Yoshikawa

    PLOS ONE　8　(7)　e70302　2013/07

    DOI： 10.1371/journal.pone.0070302 　

    ISSN： 1932-6203

  42. A population-specific uncommon variant in GRIN3A associated with schizophrenia. International-journal Peer-reviewed

    Atsushi Takata, Yoshimi Iwayama, Yasuhisa Fukuo, Masashi Ikeda, Tomo Okochi, Motoko Maekawa, Tomoko Toyota, Kazuo Yamada, Eiji Hattori, Tetsuo Ohnishi, Manabu Toyoshima, Hiroshi Ujike, Toshiya Inada, Hiroshi Kunugi, Norio Ozaki, Shinichiro Nanko, Kazuhiko Nakamura, Norio Mori, Shigenobu Kanba, Nakao Iwata, Tadafumi Kato, Takeo Yoshikawa

    Biological psychiatry　73　(6)　532-9　2013/03/15

    Publisher: 6

    DOI： 10.1016/j.biopsych.2012.10.024 　

    ISSN： 0006-3223

    More details Close

    BACKGROUND: Genome-wide association studies have successfully identified several common variants showing robust association with schizophrenia. However, individually, these variants only produce a weak effect. To identify genetic variants with larger effect sizes, increasing attention is now being paid to uncommon and rare variants. METHODS: From the 1000 Genomes Project data, we selected 47 candidate single nucleotide variants (SNVs), which were: 1) uncommon (minor allele frequency < 5%); 2) Asian-specific; 3) missense, nonsense, or splice site variants predicted to be damaging; and 4) located in candidate genes for schizophrenia and bipolar disorder. We examined their association with schizophrenia, using a Japanese case-control cohort (2012 cases and 2781 control subjects). Additional meta-analysis was performed using genotyping data from independent Han-Chinese case-control (333 cases and 369 control subjects) and family samples (9 trios and 284 quads). RESULTS: We identified disease association of a missense variant in GRIN3A (p.R480G, rs149729514, p = .00042, odds ratio [OR] = 1.58), encoding a subunit of the N-methyl-D-aspartate type glutamate receptor, with study-wide significance (threshold p = .0012). This association was supported by meta-analysis (combined p = 3.3 × 10(-5), OR = 1.61). Nominally significant association was observed in missense variants from FAAH, DNMT1, MYO18B, and CFB, with ORs of risk alleles ranging from 1.41 to 2.35. CONCLUSIONS: The identified SNVs, particularly the GRIN3A R480G variant, are good candidates for further replication studies and functional evaluation. The results of this study indicate that association analyses focusing on uncommon and rare SNVs are a promising way to discover risk variants with larger effects.

  43. 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

  44. Association study of the KCNJ3 gene as a susceptibility candidate for schizophrenia in the Chinese population Peer-reviewed

    Kazuo Yamada, Yoshimi Iwayama, Tomoko Toyota, Tetsuo Ohnishi, Hisako Ohba, Motoko Maekawa, Takeo Yoshikawa

    HUMAN GENETICS　131　(3)　443-451　2012/03

    DOI： 10.1007/s00439-011-1089-3 　

    ISSN： 0340-6717

    eISSN： 1432-1203

  45. The role of fatty acids and fatty acid binding proteins in the development of schizophrenia Peer-reviewed

    Motoko Maekawa, Chie Smmamoto

    Seikagaku　84　(10)　862-866　2012

    Publisher: 10

    ISSN： 0037-1017

  46. Ablation of Mrds1/Ofcc1 Induces Hyper-gamma-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice Peer-reviewed

    Tetsuo Ohnishi, Kazuo Yamada, Akiko Watanabe, Hisako Ohba, Toru Sakaguchi, Yota Honma, Yoshimi Iwayama, Tomoko Toyota, Motoko Maekawa, Kazutada Watanabe, Sevilla D. Detera-Wadleigh, Shigeharu Wakana, Takeo Yoshikawa

    PLOS ONE　6　(12)　e29499　2011/12

    DOI： 10.1371/journal.pone.0029499 　

    ISSN： 1932-6203

  47. 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

  48. Schizophrenia with the 22q11.2 deletion and additional genetic defects: Case history Peer-reviewed

    M. Toyosima, Motoko Maekawa, T. Toyota, Y. Iwayama, M. Arai, T. Ichikawa, M. Miyashita, T. Arinami, M. Itokawa, T. Yoshikawa

    British Journal of Psychiatry　199　(3)　245-246　2011/09

    DOI： 10.1192/bjp.bp.111.093849 　

    ISSN： 0007-1250 1472-1465

  49. Association Study of Nogo-Related Genes With Schizophrenia in a Japanese Case-Control Sample Peer-reviewed

    Daisuke Jitoku, Eiji Hattori, Yoshimi Iwayama, Kazuo Yamada, Tomoko Toyota, Mitsuru Kikuchi, Motoko Maekawa, Toru Nishikawa, Takeo Yoshikawa

    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS　156B　(5)　581-592　2011/07

    DOI： 10.1002/ajmg.b.31199 　

    ISSN： 1552-4841

    eISSN： 1552-485X

  50. Distinctive effects of arachidonic acid and docosahexaenoic acid on neural stem/progenitor cells Peer-reviewed

    Nobuyuki Sakayori, Motoko Maekawa, Keiko Numayama-Tsuruta, Takashi Katura, Takahiro Moriya, Noriko Osumi

    GENES TO CELLS　16　(7)　778-790　2011/07

    DOI： 10.1111/j.1365-2443.2011.01527.x 　

    ISSN： 1356-9597

  51. Genome-Wide Association Study of Schizophrenia in Japanese Population Peer-reviewed

    Kazuo Yamada, Yoshimi Iwayama, Eiji Hattori, Kazuya Iwamoto, Tomoko Toyota, Tetsuo Ohnishi, Hisako Ohba, Motoko Maekawa, Tadafumi Kato, Takeo Yoshikawa

    PLOS ONE　6　(6)　e20468　2011/06

    DOI： 10.1371/journal.pone.0020468 　

    ISSN： 1932-6203

  52. Understanding schizophrenia pathogenesis from developmental origins of health and disease (DOHaD)

    Takeo Yoshikawa, Motoko Maekawa

    Neuroscience Research Advances　219-226　2011/01/01

    Publisher: Nova Science Publishers, Inc.

  53. 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

  54. Evaluation of Pax6 Mutant Rat as a Model for Autism Peer-reviewed

    Toshiko Umeda, Noriko Takashima, Ryoko Nakagawa, Motoko Maekawa, Shiro Ikegami, Takeo Yoshikawa, Kazuto Kobayashi, Kazuo Okanoya, Kaoru Inokuchi, Noriko Osumi

    PLOS ONE　5　(12)　2010/12

    DOI： 10.1371/journal.pone.0015500 　

    ISSN： 1932-6203

  55. Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia Peer-reviewed

    Motoko Maekawa, Tetsuo Ohnishi, Kenji Hashimoto, Akiko Watanabe, Yoshimi Iwayama, Hisako Ohba, Eiji Hattori, Kazuo Yamada, Takeo Yoshikawa

    JOURNAL OF NEUROCHEMISTRY　115　(6)　1374-1385　2010/12

    DOI： 10.1111/j.1471-4159.2010.07039.x 　

    ISSN： 0022-3042

  56. The analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia Peer-reviewed

    Takeo Yoshikawa, Motoko Maekawa, Tetsuo Ohnishi, Kenji Hashimoto, Akiko Watanabe

    Japanese Journal of Neuropsychopharmacology　30　(5-6)　197-200　2010/11

    Publisher: 5-6

    ISSN： 1340-2544

  57. Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice Peer-reviewed

    Motoko Maekawa, Yoshimi Iwayama, Akiko Watanabe, Yayoi Nozaki, Tetsuo Ohnishi, Hisako Ohba, Manabu Toyoshima, Kei Hamazaki, Noriko Osumi, Jun Aruga, Takeo Yoshikawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　402　(2)　431-437　2010/11

    DOI： 10.1016/j.bbrc.2010.10.051 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  58. Giant Subependymoma Developed in a Patient with Aniridia: Analyses of PAX6 and Tumor-relevant Genes Peer-reviewed

    Motoko Maekawa, Hironori Fujisawa, Yoshimi Iwayama, Akira Tamase, Tomoko Toyota, Noriko Osumi, Takeo Yoshikawa

    BRAIN PATHOLOGY　20　(6)　1033-1041　2010/11

    DOI： 10.1111/j.1750-3639.2010.00406.x 　

    ISSN： 1015-6305

  59. Failure to Confirm Genetic Association of the FXYD6 Gene With Schizophrenia: The Japanese Population and Meta-Analysis Peer-reviewed

    Yasuhide Iwata, Kazuo Yamada, Yoshimi Iwayama, Ayyappan Anitha, Ismail Thanseem, Tomoko Toyota, Eiji Hattori, Tetsuo Ohnishi, Motoko Maekawa, Kazuhiko Nakamura, Katsuaki Suzuki, Hideo Matsuzaki, Kenji J. Tsuchiya, Shiro Suda, Genichi Sugihara, Kiyokazu Takebayashi, Shigeyuki Yamamoto, Keiko Iwata, Norio Mori, Takeo Yoshikawa

    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS　153B　(6)　1221-1227　2010/09

    DOI： 10.1002/ajmg.b.31095 　

    ISSN： 1552-4841

    eISSN： 1552-485X

  60. Behavioral analyses of transgenic mice harboring bipolar disorder candidate genes, IMPA1 and IMPA2 Peer-reviewed

    Tetsuo Ohnishi, Akiko Watanabe, Hisako Ohba, Yoshimi Iwayama, Motoko Maekawa, Takeo Yoshikawa

    NEUROSCIENCE RESEARCH　67　(1)　86-94　2010/05

    DOI： 10.1016/j.neures.2010.02.003 　

    ISSN： 0168-0102

  61. Association Analyses Between Brain-Expressed Fatty-Acid Binding Protein (FABP) Genes and Schizophrenia and Bipolar Disorder Peer-reviewed

    Yoshimi Iwayama, Eiji Hattori, Motoko Maekawa, Kazuo Yamada, Tomoko Toyota, Tetsuo Ohnishi, Yasuhide Iwata, Kenji J. Tsuchiya, Genichi Sugihara, Mitsuru Kikuchi, Kenji Hashimoto, Masaomi Iyo, Toshiya Inada, Hiroshi Kunugi, Norio Ozaki, Nakao Iwata, Shinichiro Nanko, Kazuya Iwamoto, Yuji Okazaki, Tadafumi Kato, Takeo Yoshikawa

    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS　153B　(2)　484-493　2010/03

    DOI： 10.1002/ajmg.b.31004 　

    ISSN： 1552-4841

    eISSN： 1552-485X

  62. 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

  63. A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient Peer-reviewed

    Motoko Maekawa, Yoshimi Iwayama, Kazuhiko Nakamura, Miho Sato, Tomoko Toyota, Tetsuo Ohnishi, Kazuo Yamada, Taishi Miyachi, Masatsugu Tsujii, Eiji Hattori, Nobuo Maekawa, Noriko Osumi, Norio Mori, Takeo Yoshikawa

    NEUROSCIENCE LETTERS　462　(3)　267-271　2009/09

    DOI： 10.1016/j.neulet.2009.07.021 　

    ISSN： 0304-3940

  64. The Alzheimer&apos;s Disease Drug Memantine Increases the Number of Radial Glia-like Progenitor Cells in Adult Hippocampus Peer-reviewed

    Takashi Namba, Motoko Maekawa, Shigeki Yuasa, Shinichi Kohsaka, Shigeo Uchino

    GLIA　57　(10)　1082-1090　2009/08

    DOI： 10.1002/glia.20831 　

    ISSN： 0894-1491

  65. Analysis of a t(18;21)(p11.1;p11.1) translocation in a family with schizophrenia Peer-reviewed

    Joanne M. A. Meerabux, Hisako Ohba, Yoshimi Iwayama, Motoko Maekawa, Sevilla D. Detera-Wadleigh, Lynn E. DeLisi, Takeo Yoshikawa

    JOURNAL OF HUMAN GENETICS　54　(7)　386-391　2009/07

    DOI： 10.1038/jhg.2009.47 　

    ISSN： 1434-5161

  66. 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

  67. NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus Peer-reviewed

    Motoko Maekawa, Takashi Namba, Eri Suzuki, Shigeki Yuasa, Shinichi Kohsaka, Shigeo Uchino

    NEUROSCIENCE RESEARCH　63　(4)　259-266　2009/04

    DOI： 10.1016/j.neures.2008.12.006 　

    ISSN： 0168-0102

  68. Development of the Mouse Amygdala as Revealed by Enhanced Green Fluorescent Protein Gene Transfer by Means of In Utero Electroporation Peer-reviewed

    Miho Soma, Hidenori Aizawa, Yoshimasa Ito, Motoko Maekawa, Noriko Osumi, Eiko Nakahira, Hitoshi Okamoto, Kohichi Tanaka, Shigeki Yuasa

    JOURNAL OF COMPARATIVE NEUROLOGY　513　(1)　113-128　2009/03

    DOI： 10.1002/cne.21945 　

    ISSN： 0021-9967

  69. A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice Peer-reviewed

    Masayuki Sekiguchi, Ko Zushida, Mikiharu Yoshida, Motoko Maekawa, Sari Kamichi, Mizuko Yoshida, Yoshinori Sahara, Shigeki Yuasa, Shin&apos;ichi Takeda, Keiji Wada

    BRAIN　132　(Pt 1)　124-135　2009/01

    DOI： 10.1093/brain/awn253 　

    ISSN： 0006-8950

  70. Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype Peer-reviewed

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

    BIOLOGICAL PSYCHIATRY　63　(7)　70S　2008/04/01

    ISSN： 0006-3223

  71. Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator Peer-reviewed

    Noriko Osumi, Hiroshi Shinohara, Keiko Numayama-Tsuruta, Motoko Maekawaa

    STEM CELLS　26　(7)　1663-1672　2008

    DOI： 10.1634/stemcells.2007-0884 　

    ISSN： 1066-5099

  72. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders Peer-reviewed

    Nobuyuki Yamasaki, Motoko Maekawa, Katsunori Kobayashi, Yasushi Kajii, Jun Maeda, Miho Soma, Keizo Takao, Koichi Tanda, Koji Ohira, Keiko Toyama, Kouji Kanzaki, Kohji Fukunaga, Yusuke Sudo, Hiroshi Ichinose, Masashi Ikeda, Nakao Iwata, Norio Ozaki, Hidenori Suzuki, Makoto Higuchi, Tetsuya Suhara, Shigeki Yuasa, Tsuyoshi Miyakawa

    MOLECULAR BRAIN　1　6　2008

    DOI： 10.1186/1756-6606-1-6 　

    ISSN： 1756-6606

  73. 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

  74. The role of Pax6 in postnatal hippocampal neurogenesis Peer-reviewed

    Maekawa Motoko, Osumi Noriko

    FUTURE MEDICAL ENGINEERING BASED ON BIONANOTECHNOLOGY, PROCEEDINGS　121-+　2006

    DOI： 10.1142/9781860948800_0013 　

  75. Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis Peer-reviewed

    M Maekawa, N Takashima, Y Arai, T Nomura, K Inokuchi, S Yuasa, N Osumi

    GENES TO CELLS　10　(10)　1001-1014　2005/10

    DOI： 10.1111/j.1365-2443.2005.00893.x 　

    ISSN： 1356-9597

Show all ︎Show first 5

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  2. ω3不飽和脂肪酸と精神疾患 核内受容体PPARαと統合失調症病態メカニズムの関連

    前川 素子

    精神神経学雑誌　(2021特別号)　S426-S426　2021/09

    Publisher: (公社)日本精神神経学会

    ISSN： 0033-2658

  3. 【精神疾患と早期ライフステージイベントの関連】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

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  4. 脳における新たな遺伝子発現制御システム「LDB2-EGR軸」と精神疾患の病態生理における役割

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    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  5. 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

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  6. 日本人研究者が発信したオリジナルな統合失調症病態仮説を統合する 神経発達期の多価不飽和脂肪酸欠乏による栄養学的統合失調症モデルマウスの検討

    前川 素子, 吉川 武男

    精神神経学雑誌　(2018特別号)　S469-S469　2018/06

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  7. 日本人研究者が発信したオリジナルな統合失調症病態仮説を統合する 神経発達期の多価不飽和脂肪酸欠乏による栄養学的統合失調症モデルマウスの検討

    前川 素子, 吉川 武男

    精神神経学雑誌　(2018特別号)　S469-S469　2018/06

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  8. Targeted re-sequencing of genes involved in H3K9 methylation machinery in autism spectrum disorders reveal a loss of function variant in SUV39H2

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    HUMAN GENOMICS　12　2018/03

    ISSN： 1473-9542

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  9. 統合失調症の病態と脳梁における脂質変動との関係解明

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    統合失調症研究　8　(1)　93　2018/03/01

  10. 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

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    日本分子生物学会年会プログラム・要旨集(Web)　41st　ROMBUNNO.2P‐0526 (WEB ONLY)　2018

  11. 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(Web)　91st　ROMBUNNO.1S10a‐02 (WEB ONLY)-02]　2018

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  12. 発達期の多価不飽和脂肪酸摂取不足による統合失調症ハイリスク状態形成メカニズムの検討

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    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　91　2018

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    日本精神神経学会総会プログラム・抄録集　114th　S.469　2018

  14. 神経発達期の多価不飽和脂肪酸欠乏による統合失調症前駆状態モデルの解析

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    脂質栄養学　26　(2)　192-192　2017/08

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  15. 頭皮の毛根細胞を用いた精神疾患関連遺伝子の発現解析

    前川素子, 大西哲生, 豊島学, 豊田倫子, 松崎秀夫, 森則夫, 吉川武男

    先進医薬研究振興財団研究成果報告集　2016　46‐47-47　2017/03/25

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    ISSN： 2189-1303

  16. 質量分析法を用いた統合失調症関連脂質の探索

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    前川 素子, 吉川 武男

    DOHaD研究　6　(1)　27-28　2017

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    More details Close

    シンポジウムⅡ「DOHaD研究最近の展開」

  18. 神経発達期の多価不飽和脂肪酸欠乏による統合失調症前駆状態モデルの解析

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  19. 【病態バイオマーカーの"いま"】 精神・神経疾患 統合失調症 統合失調症と毛根細胞の遺伝子発現

    前川 素子, 和田 唯奈

    生体の科学　67　(5)　486-487　2016/10/15

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  20. 脂肪細胞由来分子によるASD病態形成メカニズムの解明

    前川素子, 大西哲生, 松崎秀夫, 松崎秀夫, 豊島学, 豊田倫子, 森則夫, 吉川武男

    先進医薬研究振興財団研究成果報告集　2015　50‐51-51　2016/03/25

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  21. 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

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    統合失調症研究　6　(1)　81　2016/03/01

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    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　[2P1274]-[2P1274]　2015/12

    Publisher: (公社)日本生化学会

  24. DISC-M遺伝子を介した遺伝子発現ネットワークの破壊は脳の機能障害と精神障害に関連する行動欠陥を引き起こす(Disturbed gene expression networks by mediated Disrupted_in_Schizophrenia M results in malfunctioning of the brain, eliciting behavioral deficits related to mental disorders)

    大西 哲生, 新井 誠, 渡辺 明子, 大羽 尚子, 山田 一之, 島本 知英, 豊島 学, 市川 智恵, 前川 素子, 岩山 佳美, 野崎 弥生, 久野 泰子, 糸川 昌成, 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　[2P1274]-[2P1274]　2015/12

    Publisher: (公社)日本生化学会

  25. 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(Web)　88回・38回　[2P1265]-[2P1265]　2015/12

    Publisher: (公社)日本生化学会

  26. 精神疾患におけるバイオマーカー研究 毛根細胞を用いた例

    前川 素子, 吉川 武男

    精神医学　57　(11)　935-942　2015/11/15

    Publisher: (株)医学書院

    DOI： 10.11477/mf.1405205058 　

    ISSN： 0488-1281

  27. 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

    日本神経精神薬理学会プログラム・抄録集　45th　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

  28. 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　2015/08/20

    Publisher: 日本脂質栄養学会

    ISSN： 1343-4594

    eISSN： 1883-2237

  29. 自閉症バイオマーカーの探索

    前川素子

    児童青年精神医学とその近接領域　56　(3)　334-338　2015/06/01

    Publisher: (一社)日本児童青年精神医学会

    ISSN： 0289-0968

  30. 注目の遺伝子 第29回 FABP4

    前川素子, 島本知英

    分子精神医学　15　(2)　124-126　2015/04/10

    Publisher: (株)先端医学社

    ISSN： 1345-9082

  31. 自閉症早期診断マーカーとしてのASPEC1の検討

    前川素子, 渡辺明子, 大西哲生, 豊島学, 吉川武男

    先進医薬研究振興財団 2014年度 研究成果報告集　2014年度　42-42　2015/03

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 2189-1303

  32. カルボニルストレス性統合失調症の病因・病態に関わる終末糖化産物(AGEs)の探索

    豊島学, 前川素子, 大西哲生, 岡田洋平, 赤松和土, 糸川昌成, 岡野栄之, 吉川武男

    先進医薬研究振興財団 2014年度 研究成果報告集　2014年度　62-63　2015/03

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 2189-1303

  33. 染色体転座をともなう統合失調症症例の転座点に存在する転写調節因子の生物学的役割

    大西哲生, 渡辺明子, 大羽尚子, 岩山佳美, 豊島学, 島本知英, 新井誠, 山田一之, 市川智恵, 前川素子, 野崎弥生, 糸川昌成, 吉川武男

    統合失調症研究　5　(1)　83　2015/03

  34. 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, 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)　82　2015/03

  35. 頭皮の毛根細胞を用いた統合失調症診断補助バイオマーカーの開発

    前川素子, 山田和男, 豊島学, 大西哲生, 岩山佳美, 島本知英, 豊田倫子, 岡田洋平, 赤松和土, 糸川昌成, 岡野栄之, 吉川武男

    統合失調症研究　5　(1)　140　2015/03

  36. Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, and major depressive disorder

    K. Hamazaki, M. Maekawa, T. Toyota, B. Dean, T. Hamazaki, T. Yoshikawa

    PSYCHOTHERAPY AND PSYCHOSOMATICS　84　30-30　2015

    ISSN： 0033-3190

    eISSN： 1423-0348

  37. Educational Lecture : Biomarkers for Autism Spectrum Disorder

    前川 素子

    児童青年精神医学とその近接領域　56　(3)　334-338　2015

    Publisher: 日本児童青年精神医学会

    ISSN： 0289-0968

  38. 統合失調症脆弱性形成における不飽和脂肪酸欠乏によるエピジェネティック修飾の関与

    前川 素子, 木村 哲也, 浜崎 景, 渡辺 明子, 岩山 佳美, 大西 哲生, 豊島 学, 岩本 和也, 加藤 忠史, 高島 明彦, 吉川 武男

    DOHaD研究　4　(1)　83-83　2015

    Publisher: 日本DOHaD研究会

    ISSN： 2187-2597

    More details Close

    ポスター

  39. 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

  40. 自閉症バイオマーカーの探索

    前川素子, 松崎秀夫, 森則夫, 吉川武男

    日本児童青年精神医学会総会抄録集　55th　17-17　2014/10

    Publisher: (一社)日本児童青年精神医学会

    ISSN： 1349-077X

  41. 統合失調症の死後脳前頭葉における脂肪酸組成について

    浜崎景, 前川素子, 豊田倫子, BRIAN Dean, 浜崎智仁, 吉川武男

    脂質栄養学　23　(2)　172-172　2014/08/20

    Publisher: 日本脂質栄養学会

    ISSN： 1343-4594

  42. 脳特異的転写因子によるガラクトシルセラミド生合成の制御

    岡原京平, 木塚康彦, 北爪しのぶ, 太田芙美, 中嶋和紀, 平林義雄, 前川素子, 吉川武男, 谷口直之

    脂質生化学研究　56　191-193　2014/05/28

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  43. iPS細胞を用いたカルボニルストレス性統合失調症の病因解明

    豊島学, 前川素子, 大西哲生, 岡田洋平, 赤松和土, 糸川昌成, 岡野栄之, 吉川武男

    精神薬療研究年報　(46)　44-45　2014/03/24

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  44. 多価不飽和脂肪酸と統合失調症

    吉川武男, 前川素子

    日本農芸化学会大会講演要旨集(Web)　2014　WEB ONLY 4SY14-2　2014/03/05

    ISSN： 2186-7976

  45. 精神疾患の病理機構 栄養と統合失調症

    吉川武男, 前川素子

    生体の科学　65　(1)　60-64　2014/02/15

    Publisher: (公財)金原一郎記念医学医療振興財団

    DOI： 10.11477/mf.2425101578 　

    ISSN： 0370-9531

  46. 染色体転座を伴うまれな統合失調症の原因遺伝子候補DISC‐Mの機能:遺伝子改変動物を用いた解析

    大西哲生, 豊島学, 前川素子, 吉川武男

    日本脳科学会プログラム・講演抄録集　40th　43-43　2013/09

    Publisher: 日本脳科学会

  47. バイオマーカーにより階層化した統合失調症の病態解明と治療への臨床応用

    新井誠, 宮下光弘, 宮下光弘, 市川智恵, 鳥海和也, 小堀晶子, 豊田倫子, 前川素子, 大西哲生, 吉川武男, 有波忠雄, 岡崎祐士, 岡崎祐士, 久島周, 尾崎紀夫, 福本素由乙, 橋本亮太, 武田雅俊, 小池進介, 小池進介, 笠井清登, 山本博, 渡邉琢夫, 宮田敏男, 糸川昌成, 糸川昌成, 糸川昌成

    精神薬療研究年報　(45)　21-22　2013/03/21

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  48. 統合失調症特殊例(22q11.2欠失症候群)のiPS細胞樹立およびその機能解析

    豊島学, 前川素子, 大西哲生, 市川智恵, 岡田洋平, 赤松和土, 糸川昌成, 岡野栄之, 吉川武男

    精神薬療研究年報　(45)　87-88　2013/03/21

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  49. 精神疾患モデルマウスにおけるオリゴデンドロサイト前駆細胞の挙動

    前川素子, 渡辺明子, 大西哲生, 豊島学, 吉川武男

    精神薬療研究年報　(45)　59-59　2013/03/21

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  50. Brain Developmental Originhypothesis for psychoses by lack of polyunsaturated fatty acids

    Motoko Maekawa, Tetsuya Kimura, Kei Hamazaki, Akiko Watanabe, Yoshimi Iwayama, Hisako Ohba, Yasuko Hisano, Miki Bundo, Kazuya Iwamoto, Tetsuo Ohnishi, Manabu Toyoshima, Noriko Osumi, Tadafumi Kato, Akihiko Takashima, Takeo Yoshikawa

    JOURNAL OF PHARMACOLOGICAL SCIENCES　121　15P-15P　2013

    ISSN： 1347-8613

  51. 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, 前川素子, 豊田倫子, 岩山佳美, 渡邉明子, 大羽尚子, 久野泰子, 和田唯奈, 田端千夏, 座古保, 大和田祐二, 小林哲幸, 吉川武男

    日本分子生物学会年会プログラム・要旨集(Web)　36th　WEB ONLY 3P-0723　2013

  52. 統合失調症の発症における不飽和脂肪酸および脂肪酸結合タンパク質の役割

    前川素子, 島本知英, 島本知英

    生化学　84　(10)　862-866　2012/10/25

    Publisher: (公社)日本生化学会

    ISSN： 0037-1017

  53. 成長発育期の軟食と精神疾患発症との関連性について(第二報)

    野瀬 佳奈, 綿引 淳一, 山本 剛, 市川 雄大, 山田 一之, 前川 素子, 榎本 明子, 南保 友樹, 田口 智博, 小野 美樹, 美島 健二, 吉川 武男, 槇 宏太郎

    日本矯正歯科学会大会プログラム・抄録集　71回　137-137　2012/09

    Publisher: (公社)日本矯正歯科学会

  54. 離乳時からの軟食は精神疾患の発症リスクを高める可能性がある

    野瀬 佳奈, 綿引 淳一, 山本 剛, 市川 雄大, 前川 素子, 榎本 明子, 南保 友樹, 美島 健二, 吉川 武男, 槇 宏太郎

    Journal of Oral Biosciences Supplement　2012　114-114　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  55. 神経発達期における多価不飽和脂肪酸欠如の影響

    前川素子, 浜崎景, 吉川武男

    脂質栄養学　21　(2)　154-155　2012/08/20

    ISSN： 1343-4594

  56. アラキドン酸の補給は必要か? 神経発達期における多価不飽和脂肪酸欠如の影響

    前川 素子, 浜崎 景, 吉川 武男

    脂質栄養学　21　(2)　154-154　2012/08

    Publisher: 日本脂質栄養学会

    ISSN： 1343-4594

  57. 統合失調症の病態研究から創薬への展開 3.DOHaD(Developmental Origins of Health and Disease)仮説からみた統合失調症

    前川素子, 大西哲生, 吉川武男

    日本生物学的精神医学会誌　23　(2)　103-107　2012/06/25

    Publisher: 日本生物学的精神医学会

    DOI： 10.11249/jsbpjjpp.23.2_103 　

    ISSN： 2186-6619

    eISSN： 2186-6465

  58. 脂質と精神機能 統合失調症脆弱性基盤としての多価不飽和脂肪酸の役割

    前川素子, 島本知英, 島本知英

    最新精神医学　17　(3)　219-223　2012/05/25

    Publisher: (株)世論時報社

    ISSN： 1342-4300

  59. 統合失調症脆弱性形成におけるエピジェネティック修飾の関連性

    前川素子, 渡辺明子, 大西哲生, 豊島学, 吉川武男

    精神薬療研究年報　(44)　71-72　2012/03/21

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  60. Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice

    前川 素子

    脂質栄養学　21　(1)　59-65　2012/03

    Publisher: 日本脂質栄養学会

    DOI： 10.4010/jln.21.59 　

    ISSN： 1343-4594

  61. 統合失調症におけるカルボニルストレス代謝制御の分子基盤解明

    新井誠, 宮下光弘, 宮下光弘, 市川智恵, 豊田倫子, 前川素子, 大西哲生, 吉川武男, 有波忠雄, 久島周, 尾崎紀夫, 福本素由乙, 橋本亮太, 小池進介, 滝沢龍, 笠井清登, 渡邉琢夫, 山本博, 宮田敏男, 岡崎祐士, 糸川昌成, 糸川昌成, 糸川昌成

    統合失調症研究　2　(1)　109　2012/03

  62. Schizophrenia : perspective from Developmental Origins of Health and Disease (DOHaD)

    Maekawa Motoko, Ohnishi Tetsuo, Yoshikawa Takeo

    Japanese Journal of Biological Psychiatry　23　(2)　103-107　2012

    Publisher: Japanese Society of Biological Psychiatry

    DOI： 10.11249/jsbpjjpp.23.2_103 　

    ISSN： 2186-6619

    eISSN： 2186-6465

    More details Close

    Schizophrenia is a major and debilitating mental disorder that afflicts about 1% of the population worldwide. Despite intensive, multifaceted research, its exact etiology remains quite elusive. One of the prevailing hypotheses is the &quot;neurodevelopmental abnormality&quot; theory, which proposes that some schizophrenics suffer from subtle neurodevelopmental insults during fetal development, for instance, obstetric complications or maternal virus infections, resulting in biological predisposition to schizophrenia that manifest in adolescence or later. Supporting this theory is convincing epidemiological data showing that when pregnant mothers experienced malnutrition or famine (e. g. the Dutch Hunger Winter of 1994-1945 and the Chinese famine of 1959-1961), the risk of schizophrenia in their children increased by two fold. These facts could be considered in the context of DOHaD. The concept of DOHaD is well referenced in the understanding of common adult diseases such as diabetes mellitus and hypertension, but not so in the field of mental disorders. We will attempt to show how the mechanism of DOHaD could contribute at least in part to schizophrenia pathogenesis and how it can be used to develop preventive interventions for schizophrenia.

  63. 離乳時からの軟食は精神疾患の発症リスクを高める可能性がある

    野瀬佳奈, 綿引淳一, 山本剛, 市川雄大, 前川素子, 榎本明子, 南保友樹, 美島健二, 吉川武男, 槇宏太郎

    Journal of Oral Biosciences Supplement (Web)　2012　ROMBUNNO.P1‐29 (WEB ONLY)　2012

    ISSN： 2187-9109

  64. 成長発育期の軟食と精神疾患発症との関連性について(第二報)

    野瀬佳奈, 綿引淳一, 山本剛, 市川雄大, 山田一之, 前川素子, 榎本明子, 南保友樹, 田口智博, 小野美樹, 美島健二, 吉川武男, 槇宏太郎

    日本矯正歯科学会大会プログラム・抄録集　71st　137　2012

  65. ―脳の機能と統合失調症―新たな診断と治療への展望―II カルボニルストレス

    新井誠, 小池進介, 前川素子, 宮下光弘, 市川智恵, 吉川武男, 笠井清登, 糸川昌成

    精神科治療学　26　(12)　1589-1596　2011/12/19

    ISSN： 0912-1862

  66. 【脳の機能と統合失調症-新たな診断と治療への展望-II】 カルボニルストレス

    新井 誠, 小池 進介, 前川 素子, 宮下 光弘, 市川 智恵, 吉川 武男, 笠井 清登, 糸川 昌成

    精神科治療学　26　(12)　1589-1596　2011/12

    Publisher: (株)星和書店

    ISSN： 0912-1862

  67. 現代社会とうつ病 6 遺伝子発現からみたうつ病の神経科学

    前川素子, 豊島学, 吉川武男

    最新医学　66　(10)　2400-2405　2011/10/10

    Publisher: 最新医学社

    ISSN： 0370-8241

  68. 現代社会とうつ病 遺伝子発現からみたうつ病の神経科学

    前川 素子, 豊島 学, 吉川 武男

    最新医学　66　(10)　2400-2405　2011/10

    Publisher: (株)最新医学社

    ISSN： 0370-8241

  69. 食生活への介入で精神疾患を予防できるか? 統合失調症脆弱性基盤としての多価不飽和脂肪酸の役割

    前川 素子

    精神神経学雑誌　(2011特別)　S-271　2011/10

    Publisher: (公社)日本精神神経学会

    ISSN： 0033-2658

  70. 精神疾患と脂肪酸をつなぐ分子としてのFABP

    前川素子

    脂質栄養学　20　(2)　111　2011/08/20

    ISSN： 1343-4594

  71. 精神疾患や脳機能と脂質栄養 精神疾患と脂肪酸をつなぐ分子としてのFABP

    前川 素子

    脂質栄養学　20　(2)　111-111　2011/08

    Publisher: 日本脂質栄養学会

    ISSN： 1343-4594

  72. Mice Deficient in a Gene Encoding a Transcriptional Regulator Exhibit Multiple Behavioral Deficits Reminiscent of Schizophrenia

    Tetsuo Ohnishi, Kazuyuki Yamada, Makoto Arai, Akiko Watanabe, Hisako Ohba, Fumiko Arima, Tomoe Ichikawa, Guy Ornthanalais, Yoshimi Iwayama, Motoko Maekawa, Kazuo Yamada, Mitsuhiro Miyashita, Niall Murphy, Toshiya Manabe, Masanari Itokawa, Takeo Yoshikawa

    BIOLOGICAL PSYCHIATRY　69　(9)　222S-222S　2011/05

    ISSN： 0006-3223

  73. マウス系統間の母乳成分比較:精神疾患予防物質のスクリーニング

    前川素子, 渡辺明子, 橋本謙二, 浜崎景, 小林俊秀, 吉川武男

    日本生物学的精神医学会誌　22　(Supplement)　81　2011/05

    ISSN： 2186-6619

  74. ゲノムワイド関連解析(GWAS)による統合失調症シグナルパスウェイの同定

    山田和男, 岩山佳美, 服部栄治, 岩本和也, 豊田倫子, 大西哲生, 大羽尚子, 前川素子, 加藤忠史, 吉川武男

    日本生物学的精神医学会誌　22　(Supplement)　73　2011/05

    ISSN： 2186-6619

  75. 脳発達期不飽和脂肪酸投与による精神疾患発症・予防メカニズムの解明

    前川素子, 渡辺明子, 大西哲生, 吉川武男

    精神薬療研究年報　(43)　81-82　2011/03/22

    ISSN： 1346-1702

  76. 脳発達期不飽和脂肪酸投与による精神疾患発症・予防メカニズムの解明

    前川 素子, 渡辺 明子, 大西 哲生, 吉川 武男

    精神薬療研究年報　(43)　81-82　2011/03

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  77. 染色体転座を伴う統合失調症―症例における異常候補遺伝子ノックアウトマウスの表現型

    大西哲生, 山田一之, 有馬史子, 新井誠, 渡辺明子, 大羽尚子, ガイ オルンサナライ, 市川智恵, 岩山佳美, 山田和男, 宮下光弘, 前川素子, 真鍋俊也, マーフィー ニール, 糸川昌成, 吉川武男

    統合失調症研究　1　(1)　85　2011/03

  78. Distinctive effects of arachidonic acid and docosahexaenoic acid on neural stem/progenitor cells

    Nobuyuki Sakayori, Motoko Maekawa, Keiko Numayama-Tsuruta, Takashi Katura, Takahiro Moriya, Noriko Osumi

    NEUROSCIENCE RESEARCH　71　E228-E228　2011

    DOI： 10.1016/j.neures.2011.07.995 　

    ISSN： 0168-0102

  79. Lack of long-chain polyunsaturated fatty acids during developmental stage may increase the risk of schizophrenia

    Motoko Maekawa, Kei Hamazaki, Takeo Yoshikawa

    NEUROSCIENCE RESEARCH　71　E29-E29　2011

    DOI： 10.1016/j.neures.2011.07.124 　

    ISSN： 0168-0102

  80. 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

  81. 統合失調症脆弱性基盤としての多価不飽和脂肪酸の役割

    前川素子

    日本精神神経学会総会プログラム・抄録集　107th　S.271　2011

  82. 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

    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　83回・33回　2T15-2　2010/12

    Publisher: (公社)日本生化学会

  83. 【統合失調症グルタミン酸系治療薬の臨床開発と基礎研究】 統合失調症グルタミン酸仮説におけるSHMT1遺伝子

    吉川 武男, 前川 素子, 大西 哲生, 橋本 謙二, 渡邊 明子

    日本神経精神薬理学雑誌　30　(5-6)　197-200　2010/11

    Publisher: (一社)日本神経精神薬理学会

    ISSN： 1340-2544

  84. The analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia

    Takeo Yoshikawa, Motoko Maekawa, Tetsuo Ohnishi, Kenji Hashimoto, Akiko Watanabe

    Japanese Journal of Neuropsychopharmacology　30　(5-6)　197-200　2010/11

    ISSN： 1340-2544

  85. Brain science (82) NG2[(+)] cells and psychiatric illnesses

    吉川 武男, 豊島 学, 前川 素子

    Psychiatry　17　(4)　401-406　2010/10/28

    Publisher: 科学評論社

    ISSN： 1347-4790

  86. Brain Science NG2陽性細胞(ポリデンドロサイト)と精神疾患

    吉川 武男, 豊島 学, 前川 素子

    精神科　17　(4)　401-406　2010/10

    Publisher: (有)科学評論社

    ISSN： 1347-4790

  87. 成長発育期の軟食は精神疾患の発症リスクを高める可能性がある

    綿引 淳一, 榎本 明子, 野瀬 佳奈, 前川 素子, 南保 友樹, 田口 智博, 小野 美樹, 松葉 由紀夫, 西道 隆臣, 吉川 武男, 山口 陽子, 槇 宏太郎

    日本矯正歯科学会大会プログラム・抄録集　69回　268-268　2010/09

    Publisher: (公社)日本矯正歯科学会

  88. 神経系前駆細胞の増殖と分化におけるアラキドン酸とドコサヘキサエン酸の効果の解析(The effects of arachidonic acid and docosahexaenoic acid on neural stem/progenitor cells)

    酒寄 信幸, 前川 素子, 沼山 恵子, 大隅 典子

    神経化学　49　(2-3)　502-502　2010/08

    Publisher: 日本神経化学会

    ISSN： 0037-3796

  89. 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

  90. プレパルス抑制と統合失調症におけるSHMT1遺伝子の関与の可能性(Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia)

    吉川 武男, 前川 素子, 大西 哲生, 橋本 謙二, 渡邉 明子, 岩山 佳美, 大羽 尚子, 服部 栄治, 山田 和男

    神経化学　49　(2-3)　588-588　2010/08

    Publisher: 日本神経化学会

    ISSN： 0037-3796

  91. 離乳直後からの軟食は、プレパルス抑制試験の低下を引き起こす(Soft-diet feeding reduces prepulse inhibition in young mice after weaning)

    綿引 淳一, 榎本 明子, 野瀬 佳奈, 南保 友樹, 松葉 由紀夫, 前川 素子, 吉川 武男, 西道 隆臣, 山口 陽子, 槇 宏太郎

    神経化学　49　(2-3)　675-675　2010/08

    Publisher: 日本神経化学会

    ISSN： 0037-3796

  92. Elevated SHMT1 Level Leads to Lowed Glycine Availability and Reduced Prepulse Inhibition in Mice and is Associated with Schizophrenia: A New Molecule Relevant to NMDA Theory of Schizophrenia

    Takeo Yoshikawa, Motoko Maekawa, Tetsuo Ohnishi, Kenji Hashimoto, Akiko Watanabe, Yoshimi Iwayama, Hisako Ohba

    BIOLOGICAL PSYCHIATRY　67　(9)　73S-73S　2010/05

    ISSN： 0006-3223

  93. 統合失調症と生活習慣 ω‐3系不飽和脂肪酸と統合失調症

    吉川武男, 前川素子

    Schizophrenia Front　11　(1)　13-17　2010/03/31

    ISSN： 1345-8639

  94. 不飽和脂肪酸投与による統合失調症の予防法の検討

    前川素子, 渡辺明子, 大西哲生, 吉川武男

    精神薬療研究年報　(42)　93-94　2010/03/23

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  95. 統合失調症・気分障害 4.統合失調症・気分障害とFABP/Fabp遺伝子

    前川素子, 吉川武男

    実験医学　28　(5)　740-744　2010/03/15

    ISSN： 0288-5514

  96. 【脳神経系の情報伝達と疾患 さまざまなシグナル伝達因子の異常が引き起こす精神疾患・発達障害・神経変性疾患のメカニズム】 統合失調症・気分障害 統合失調症・気分障害とFABP/Fabp遺伝子

    前川 素子, 吉川 武男

    実験医学　28　(5)　740-744　2010/03

    Publisher: (株)羊土社

    ISSN： 0288-5514

  97. 不飽和脂肪酸投与による統合失調症の予防法の検討

    前川 素子, 渡辺 明子, 大西 哲生, 吉川 武男

    精神薬療研究年報　(42)　93-94　2010/03

    Publisher: (公財)先進医薬研究振興財団

    ISSN： 1346-1702

  98. 【統合失調症と生活習慣】 ω-3系不飽和脂肪酸と統合失調症

    吉川 武男, 前川 素子

    Schizophrenia Frontier　11　(1)　13-17　2010/03

    Publisher: (株)メディカルレビュー社

    ISSN： 1345-8639

  99. Behavioral analyses of transgenic mice harboring bipolar disorder candidate genes, IMPA1 and IMPA2

    T. Ohnishi, A. Watanabe, H. Ohba, Y. Iwayama, M. Maekawa, J. -i. Semba, T. Yoshikawa

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY　13　65-65　2010

    ISSN： 1461-1457

  100. 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

  101. Soft-diet feeding reduces prepulse inhibition in young mice after weaning

    Junichi Watahiki, Akiko Enomoto, Kana Nose, Tomoki Nampo, Yukio Matsuba, Motoko Maekawa, Takeo Yoshikawa, Takaomi Saido, Yoko Yamaguchi, Koutaro Maki

    NEUROSCIENCE RESEARCH　68　E314-E314　2010

    DOI： 10.1016/j.neures.2010.07.1396 　

    ISSN： 0168-0102

  102. Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia

    Takeo Yoshikawa, Motoko Maekawa, Tetsuo Ohnishi, Kenji Hashimoto, Akiko Watanabe, Yoshimi Iwayama, Hisako Ohba, Eiji Hattori, Kazuo Yamada

    NEUROSCIENCE RESEARCH　68　E201-E201　2010

    DOI： 10.1016/j.neures.2010.07.2462 　

    ISSN： 0168-0102

  103. The effects of arachidonic acid and docosahexaenoic acid on neural stem/progenitor cells

    Nobuyuki Sakayori, Motoko Maekawa, Keiko Numayama-Tsuruta, Noriko Osumi

    NEUROSCIENCE RESEARCH　68　E90-E90　2010

    DOI： 10.1016/j.neures.2010.07.165 　

    ISSN： 0168-0102

  104. 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

  105. 成長発育期の軟食は精神疾患の発症リスクを高める可能性がある

    綿引淳一, 榎本明子, 野瀬佳奈, 前川素子, 南保友樹, 田口智博, 小野美樹, 松葉由紀夫, 西道隆臣, 吉川武男, 山口陽子, 槇宏太郎

    日本矯正歯科学会大会プログラム・抄録集　69th　268　2010

  106. ALZHEIMER&apos;S DISEASE DRUG "MEMANTINE" PROMOTES NEUROGENESIS AND PROGENITOR CELL SELF-RENEWING IN ADULT MOUSE HIPPOCAMPUS

    T. Namba, M. Maekawa, S. Yuasa, S. Uchino, S. Kohsaka

    JOURNAL OF NEUROCHEMISTRY　110　28-28　2009/09

    ISSN： 0022-3042

  107. 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

  108. 発達期(特に胎児期)の低栄養が精神機能に与える影響

    前川素子, 吉川武男, 大隅典子

    週刊日本医事新報　(4441)　39-42　2009/06/06

    Publisher: 日本医事新報社

    ISSN： 0385-9215

  109. 基礎医学から 発達期(特に胎児期)の低栄養が精神機能に与える影響

    前川 素子, 吉川 武男, 大隅 典子

    日本医事新報　(4441)　39-42　2009/06/06

    Publisher: 日本医事新報社

    ISSN： 0385-9215

  110. Neurodevelopmental hypothesis of schizophrenia and involvement of essential fatty acid

    吉川 武男, 渡辺 明子, 前川 素子

    Journal of lipid nutrition　18　(1)　81-91　2009/03/31

    Publisher: 日本脂質栄養学会

    DOI： 10.4010/jln.18.81 　

    ISSN： 1343-4594 1883-2237

  111. NMDA receptor and schizophrenia - From the perspective of neurogenesis

    Motoko Maekawa, Takashi Namba, Shigeo Uchino, Shinichi Kohsaka, Takeo Yoshikawa

    NEUROSCIENCE RESEARCH　65　S8-S8　2009

    DOI： 10.1016/j.neures.2009.09.1512 　

    ISSN： 0168-0102

  112. Upregulation of PEDF by the Alzheimer&apos;s disease drug memantine is involved in the increased neurogenesis of adult mouse hippocampus

    Takashi Namba, Motoko Maekawa, Takeshi Yabe, Shigeki Yuasa, Shigeo Uchino, Shinichi Kohsaka

    NEUROSCIENCE RESEARCH　65　S103-S103　2009

    DOI： 10.1016/j.neures.2009.09.452 　

    ISSN： 0168-0102

  113. Neurodevelopmental hypothesis of schizophrenia and involvement of essential fatty acid

    Yoshikawa Takeo, Watanabe Akiko, Maekawa Motoko

    Journal of Lipid Nutrition　18　(1)　81-91　2009

    Publisher: Japan Society for Lipid Nutrition

    ISSN： 1343-4594

    More details Close

    Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis, on 1010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected 6 major loci for PPI. A promising candidate on the chromosome 10-QTL was &lt;I&gt;Fabp7&lt;/I&gt; (fatty acid binding protein 7, brain), a gene with functional links to the NMDA receptor and expression in neural stem/progenitor cells in developmental stage. &lt;I&gt;Fabp7&lt;/I&gt;-deficient mice indeed showed decreased PPI. A quantitative complementation test supported &lt;I&gt;Fabp7&lt;/I&gt; as a potential PPI-QTL gene. Disruption of &lt;I&gt;Fabp7&lt;/I&gt; attenuated neurogenesis in vivo. Human &lt;I&gt;Fabp7&lt;/I&gt; showed genetic association with schizophrenia. FABP7 is known to have high affinity for polyunsaturated fatty acids, in particular docosahexaenoic acid. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental and nutritional issues of schizophrenia pathology.

  114. マウス系統間のプレパルス抑制の違いはD‐セリン代謝系に関係する

    前川素子, 橋本謙二, 吉川武男

    日本脳科学会プログラム・講演抄録集　36th　23　2009

  115. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain

    前川 素子

    Japanese journal of molecular psychiatry　9　(1)　62-64　2009/01

    Publisher: 先端医学社

    ISSN： 1345-9082

  116. 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

    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　81回・31回　3T5-1　2008/11

    Publisher: (公社)日本生化学会

  117. 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

  118. 注目の遺伝子 第2回 FABP7遺伝子

    前川素子, 大隅典子

    分子精神医学　8　(3)　260-263　2008/07/10

    Publisher: 先端医学社

    ISSN： 1345-9082

  119. 注目の遺伝子 FABP7遺伝子

    前川 素子, 大隅 典子

    分子精神医学　8　(3)　260-263　2008/07

    Publisher: (株)先端医学社

    ISSN： 1345-9082

  120. Alzheimer&apos;s disease drug "memantine" promotes neurogenesis in adult mouse hippocampus

    Takashi Namba, Motoko Maekawa, Eri Suzuki, Shigeki Yuasa, Shigeo Uchino, Shinichi Kohsaka

    NEUROSCIENCE RESEARCH　61　S169-S169　2008

    ISSN： 0168-0102

  121. Fatty acid binding proteins play crucial roles in hippocampal neurogenesis

    Miho Matsumata, Motoko Maekawa, Noriko Osumi

    NEUROSCIENCE RESEARCH　61　S24-S24　2008

    ISSN： 0168-0102

  122. 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

  123. アラキドン酸の生後海馬神経新生に対する効果

    前川素子, 吉川武男

    日本脳科学会プログラム・講演抄録集　35th　31　2008

  124. NMDA受容体阻害剤の成体海馬神経細胞新生に対する影響

    難波隆志, 前川素子, 湯浅茂樹, 内野茂夫, 高坂新一

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集　23rd　68　2008

  125. 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

    Inflammation and Regeneration　27　(4)　385-385　2007/07

    Publisher: 日本炎症・再生医学会

    ISSN： 1880-9693

  126. 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

  127. 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

  128. Alpha-CaMKII deficiency causes dysregulated behaviours and immature dentate gyrus

    Nobuyuki Yamasaki, Motoko Maekawa, Katsunori Kobayashi, Yasushi Kajii, Jun Maeda, Miho Soma, Keizo Takao, Kouji Kanzaki, Hidenori Suzuki, Makoto Higuchi, Tetsuya Suhara, Shigeki Yuasa, Tsuyoshi Miyakawa

    NEUROSCIENCE RESEARCH　58　S182-S182　2007

    ISSN： 0168-0102

  129. マウスKIAA長鎖cDNAがコードする蛋白質に対して網羅的に作製された抗体の神経科学研究への応用

    湯浅茂樹, 前川素子, 加藤怜子, 相馬美歩, 島田希代, 小原令子, 岡崎規理子, 古閑比佐志

    生化学　1W19-4　2007

    ISSN： 0037-1017

  130. 遺伝環境相互作用 神経新生に対する遺伝環境相互作用と精神疾患

    前川素子, 大隅典子

    分子精神医学　6　(2)　127-134　2006/04/10

    ISSN： 1345-9082

  131. 【遺伝環境相互作用】 神経新生に対する遺伝環境相互作用と精神疾患

    前川 素子, 大隅 典子

    分子精神医学　6　(2)　127-134　2006/04

    Publisher: (株)先端医学社

    ISSN： 1345-9082

  132. 神経新生に対する遺伝環境相互作用と精神疾患 (特集 遺伝環境相互作用)

    前川 素子, 大隈 典子

    分子精神医学　6　(2)　127-134　2006/04

    Publisher: 先端医学社

    ISSN： 1345-9082

  133. 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

  134. ミニレビュー 神経新生における転写因子Pax6の役割

    前川 素子, 大隅 典子

    Clinical Neuroscience　23　(7)　828-828　2005/07

    Publisher: (株)中外医学社

    ISSN： 0289-0585

  135. The role of transcription factor Pax6 in the nerve new birth.

    前川素子, 大隅典子

    Clin Neurosci　23　(7)　828　2005/07/01

    ISSN： 0289-0585

  136. 統合失調症のニューロン新生障害仮説

    大隅 典子, 前川 素子, 櫻井 勝康

    実験医学　22　(16)　2312-2317　2004/11

    Publisher: (株)羊土社

    ISSN： 0288-5514

  137. 統合失調症のニューロン新生障害仮説

    大隅典子, 前川素子, 桜井勝康

    実験医学　22　(16)　2312-2317　2004/11/01

    ISSN： 0288-5514

  138. 高次脳機能発達障害の分子神経生物学的基盤 ニューロン新生低下と行動異常の関連(Molecular-neurobiological basis for the developmental defects of higher brain function: A potential link between impaired neurogenesis and behavior abnormalities)

    大隅 典子, 前川 素子, 高嶋 記子, 池上 史郎, 井ノ口 馨

    神経化学　43　(2-3)　349-349　2004/08

    Publisher: 日本神経化学会

    ISSN： 0037-3796

  139. 海馬神経新生へのPax6の関与(Pax6 haploinsufficiency impairs hippocampal neurogenesis)

    前川 素子, 湯浅 茂樹, 大隅 典子

    神経化学　43　(2-3)　484-484　2004/08

    Publisher: 日本神経化学会

    ISSN： 0037-3796

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Industrial Property Rights 6

  1. 発毛組成物

    吉川 武男, 前川 素子, 大西 哲生

    Property Type: Patent

  2. 神経再生剤

    紺谷 昌仙, 石倉 義之, 大隅 典子, 前川 素子

    Property Type: Patent

  3. 神経再生のための飲食品

    紺谷 昌仙, 石倉 義之, 大隅 典子, 前川 素子

    特許第6104356号

    Property Type: Patent

  4. 精神関連疾患の検査方法および検査キット

    吉川 武男, 前川 素子, 森 則夫, 松▲崎▼ 秀夫, 中村 和彦

    Property Type: Patent

  5. 神経再生剤

    紺谷 昌仙, 石倉 義之, 大隅 典子, 前川 素子

    Property Type: Patent

  6. 神経再生剤

    紺谷 昌仙, 石倉 義之, 大隅 典子, 前川 素子

    特許第6150735号

    Property Type: Patent

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Research Projects 19

  1. Mechanisms Linking Maternal Undernutrition to Schizophrenia Risk in Offspring via Metabolic Dysregulation

    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

    2025/04/01 - 2028/03/31

  2. Exploring the Mechanisms of Schizophrenia Induced by Malnutrition During Brain 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

  3. 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

  4. 脳発達期の栄養恒常性破綻による統合失調症病態形成メカニズムの解明

    前川 素子, 岩本 和也, 中谷 明弘, 大西 哲生, 高田 篤

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  5. 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 Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: Tohoku University

    2020/10/27 - 2025/03/31

  6. 脂肪組織由来生理活性物質による自閉症病態形成メカニズムの解明

    前川 素子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的研究(萌芽)

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2022/06/30 - 2024/03/31

  7. 一細胞遺伝子発現解析の実現による統合失調症病態メカニズム解明と創薬への応用

    前川 素子

    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: 国立研究開発法人理化学研究所

    2018/04/01 - 2021/03/31

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    ＜研究目的＞PPARAにより発現制御される遺伝子を探索するため、PPARAアゴニスト投与マウスから脳組織を採取してRNA-seq解析を行う。 ＜令和2年度の研究実績＞8週齢のB6Jマウスに対して、PPARA選択的アゴニストfenofibrate (100 mg/kg/day)、対照群としてcorn oil (vehicle)を1日1回、2週間の経口投与を行った。fenofibrate投与マウスと対照群（corn oil投与群）から採取した前頭前野を用いてRNA-seq解析を実施したところ、1,385 (10.8 %)の遺伝子がdownregulateされ、1,240 (9.73 %)の遺伝子がupregulateされた(p < 0.05, log2 |fold change| > 0.1 or < －0.1)。この2.625遺伝子についてIPA解析を行うと、発現に差のある遺伝子がシナプス形成伝達経路に有意に濃縮されていることがわかった。シナプス形成伝達経路に含まれる遺伝子について、WEBツールPPRE SEARCH (http://www.classicrus.com/PPRE/) により転写開始点から上流2000 bp以内のPPREの存在について検索したところ、全ての遺伝子でPPREが存在していたことから、これらのシナプス形成伝達経路に含まれる遺伝子がPPARAによって制御される可能性が示唆された。 ＜意義、重要性＞PPARAはシナプス伝達経路関連遺伝子を調節することによって、疾患の発症に関与することが考えられた。今後、PPARAによる転写制御機構についてより詳しく検討する必要がある。その際には、脳組織や神経系培養細胞を用いたChIP-seq解析などのアプローチが有用と考えられる。

  8. Exploration and Identification of schizophrenia related lipid molecules

    Shimamoto Chie, Ohnishi Tetsuo, Maekawa Motoko, Iwayama Yoshimi, Balan Shabeesh, Esaki Kayoko, Watanabe Akiko, Ohba Hisako, Toyota Tomoko, Dean Brian, Yoshikawa Takeo

    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: Institute of Physical and Chemical Research

    2016/04/01 - 2019/03/31

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    In this study, we hypothesized that abnormal lipid homeostasis is involved in the pathology of schizophrenia. First, we analyzed the mouse model (Fabp7 KO mouse) using imaging mass spectrometry. We found that they showed tended to have an altered abundance in some kinds of phospholipids in the schizophrenia-related brain regions. Next, we performed lipid analysis using liquid chromatography and gene expression analyses using the postmortem corpus callosum from schizophrenics and unaffected controls. We found that 20 lipid species were reduced in schizophrenia and the expressions of 10 lipid metabolism-related genes and 7 transcription factor genes which potentially act as an upstream regulator(s) for those lipid metabolism-related genes were dysregulated in schizophrenia. Our findings suggest the possibility that abnormal lipid synthesis/remodeling may be molecular underpinnings for the corpus callosum abnormalities reported in schizophrenia.

  9. Pathology of schizophrenia by regulation of oligodendrocyte related-genes Competitive

    Maekawa Motoko, YOSHIKAWA Takeo, OHNISHI Tetsuo, TOYOSHIMA Manabu, SHIMAMOTO Chie

    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: Institute of Physical and Chemical Research

    2015/04/01 - 2018/03/31

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    We hypothesized that specific nuclear receptors regulate expressions of multiple oligodendrocyte-related genes and that they are implicated in the schizophrenia pathology. We found that RXR agonist bexarotene increased the expression levels of the oligodendrocyte-related genes and that the RXR antagonist HX531 decreased them in the OLP6 cells (the oligodendrocyte cell line). The RXR agonist bexarotene also elicited a trend toward increased expression of those genes in wild type mice. Treatment of mice with bexarotene tended to suppress the hyper-locomotive responses induced by MK-801. Notably, expressions of the nuclear receptor genes were found to be down-regulated in hair follicles cells from individuals affected with schizophrenia. Taken together, these results suggest that the RXR system regulates oligodendrocyte-related genes, thereby playing a crucial role in the schizophrenia pathophysiology.

  10. A role of MPST in the pathophysiology of psychiatric illnesses, in particular schizophrenia

    YOSHIKAWA TAKEO

    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: Institute of Physical and Chemical Research

    2014/04/01 - 2017/03/31

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    We previously identified elevated levels of Mpst, a hydrogen sulfide (H2S)-producing enzyme, in an inbred mouse model for schizophrenia. In this study, biochemical analyses revealed increased contents of free H2S and polysulfides (H2Sn), and bound sulfane sulfur, an intracellular storage molecule of H2S, in the model inbred. In keeping with mouse data, we observed up-regulation of corresponding genes in schizophrenia-derived postmortem brain samples, neurospheres differentiated from iPS cells, and scalp hair follicles, with the last issue further pursued as a potential biomarker. Dysregulated DNA methylation status of responsible genes was thought to underlie a mechanism. An animal study suggested an inflammatory insult in the brain development stage as a cause of epigenetics changes. These data suggest that elevated sulfide stress (H2S production) could constitute a novel schizophrenia pathophysiology.

  11. 次世代シークエンサーによる統合失調症脆弱性HLA領域の配列決定

    山田 和男, 吉川 武男, 大西 哲生, 前川 素子, 豊島 学

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 国立研究開発法人理化学研究所

    2014/04/01 - 2017/03/31

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    染色体6p21.3-22.1に存在する主要組織適合遺伝子複合体 (MHC）領域は、最も有力な統合失調症関連座位とされながら、進化の過程で遺伝子重複を繰り返し非常に複雑な染色体構造を持つに至った領域特異性から、従来のSNP解析・シークエンス法に基づくゲノム解析は困難であった。一方、新しい研究手法である次世代シークエンサー(NGS)では、phase ambiguity のない完全な塩基配列をhigh throughputに取得できることから、これまでの実験的障壁の打破が期待できる。 そこで、本研究課題では当該領域が持つ統合失調症脆弱性の包括的な解明を目指したNGSによるMHC領域の網羅的なゲノム解析を行うこととし、平成26年度は解析手法を確立すべく2つの実験系による検討を行った。 方法1はIllumina Nexteraを用いて、免疫機能に重要な役割を果たすと考えられているHLA-A, -C, -B, -DRB1, -DQB1, -DPB1領域について、当該6領域のlong-PCRを行い、次にNextera DNA Sample Preparation Kit（Illumina）を用いたライブラリー作成を行った。方法2ではSeqCap EZ Choice Library（Roche-NimbleGen）を用いて、ヒトMHC全4.97Mb領域をターゲットとしたライブラリー調整を行った。いずれも配列解析はNGS（MiSeq、Illumina）を用いて、2x250bp paired-end readsで行った。 さらに、疾患脆弱性が示唆された変異領域については、詳細な遺伝統計学的解析および統合失調症罹患者死後脳での発現解析を行った。その結果、疾患関連候補遺伝子として検討した3遺伝子のうち、1遺伝子について統合失調症群での発現変化の可能性が示唆された。

  12. Elucidation of pathologic mechanism using iPS cells derived from schizophrenia patients

    YOSHIKAWA TAKEO, KOBAYASHI Toshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Institution: Institute of Physical and Chemical Research

    2012/06/28 - 2017/03/31

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    We studied iPS cells derived from schizophrenia with the microdeletion of chromosome 22q11.2 and with impaired GLO1 gene whose protein product is involved in the scavenging of carbonyl stress. In these studies, we focused on the schizophrenia theory of “abnormal neurodevelopment”.We observed disturbed differentiation efficiencies in patients’iPS cell-derived neurospheres and neurons. Those defects of neural differentiations were partially rescued by an inhibitor of p38 (for 22q11.2 deletion) or by scavengers of carbonyl stress (for GLO1 mutation), suggesting an importance of rectifying abnormal neural differentiations in early neurodevelopmental stage. We could also confirm that abnormal neural differentiations are seen in patients’ postmortem brains, by examining the expression ratio of neuronal and glial markers.

  13. Comprehensive understanding of pathobiology of mental illnesses by examining relationship between polyunsaturated fatty acids and oligodendrocyte precursor cells

    YOSHIKAWA TAKEO, YAMADA Kazuo, MAEKAWA Motoko, HAMASAKI Kei

    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: The Institute of Physical and Chemical Research

    2011/04/01 - 2014/03/31

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    One of the cogent hypotheses of schizophrenia etiology is "neurodevelopmental abnormality theory", which proposes that subtle insults during brain developmental period"underlies the susceptibility of schizophrenia. We tested this theory by raising mice with polyunsaturated fatty acid (PUFA)-deficient diet during neurodevelopmental stage (PUFA(-)-mice). The PUFA(-)-mice displayed behavioral phenotypes reminiscent of early stage of schizophrenia. Interestingly, myelin-related genes were down-regulated in the frontal cortex of PUFA(-)-mice as in the postmortem brains of schizophrenia. We revealed that the above downregulations are caused by decreased expressions of transcription factor genes, TF-A and TF-B. The promoter regions of TF-A and TF-B from the brains of PUFA(-)-mice showed elevated DNA methylation, which probably lead to the lowered expressions of TF-A and TF-B.

  14. The function and mechanism of GABAergic signaling in schizophrenia

    YAMADA Kazuo, YOSHIKAWA Takeo, OHNISHI Tetsuo, MAEKAWA Motoko, TOYOSHIMA Manabu

    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: The Institute of Physical and Chemical Research

    2011/04/01 - 2014/03/31

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    Studies have provided evidence for abnormalities of the GABAergic system in schizophrenia. Cannabinoid receptors may play a role in modulating GABAergic neurons. In this study, we have performed the genetic analysis of the GABAergic neural transmission and the cannabinoid pathway in the pathophysiology of schizophrenia. We examined the association of genetic variation with the disease and the alteration of gene expression in post-mortem schizophrenic brain. We found the evidence that a number of the genes in these signaling pathways are related to the disease. In addition, we conducted a series of behavioral tests in knockout mice. In behavioral experiments, knockout mice of the genes have multiple schizophrenia-like defects such as hypoactivity and reduced social interaction. The results implicate GABAergic and cannabinoid-related dysfunctions as a key component of the molecular mechanism of schizophrenia.

  15. Analysis of iPS cells from patients with 22q11.2 deletion and schizophrenia

    YOSHIKAWA Takeo, MAEKAWA Motoko, TOYOSHIMA Manabu

    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: The Institute of Physical and Chemical Research

    2011 - 2012

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    We established iPS cells from two patients with 22q11.2 deletion and schizophrenia. Control iPS cells were from two normal subjects. We differentiated them into neurospheres (NS). Using these NS, we performed cDNA microarray analysis and found that DGCR8 gene, which is responsible for miRNA processing, is down-regulated in the NS from patients. Then we did miRNA chip analysis and revealed that the expressions of miRNAs relevant to differentiation from NS to neurons are dysregulated.

  16. -Screening of nutrients for schizophrenia prevention by comparison of breast milk between mouse strains.seika Competitive

    MAEKAWA Motoko

    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: The Institute of Physical and Chemical Research

    2011 - 2012

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    Schizophrenia is a debilitating mental disorder that afflicts about 1% of the population worldwide. Despite intensive and multifaceted research, its exact etiology remains largely elusive. The neurodevelopmental hypothesis of schizophrenia suggests that subtle disturbances occurred in early brain development increases the risk of later schizophrenia development. Accordingly, various prenatal and perinatal risk factors have been linked to schizophrenia, including exposures related to infection, malnutrition and obstetric complications. Currently, we have revisited the importance of relevant epidemiological data: “Dutch Hunger Winter in 1944 to 1945” and “A massive 1959-1961 famine in China”. These epidemiological data show that when pregnant mothers experienced malnutrition or famine, the risk of schizophrenia in their children increased by about two fold. Therefore, we addressed the potential nutritional factors of mental disorders including schizophrenia by using mice.

  17. FABP遺伝子を起点とした機能性精神障害と不飽和脂肪酸の関連についての研究

    吉川 武男, 服部 栄治, 前川 素子, 岩山 佳美

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的萌芽研究

    Category: 挑戦的萌芽研究

    Institution: 独立行政法人理化学研究所

    2009 - 2010

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    研究目的として以下の5項目をあげ、研究を実施した:1.FABP7躁うつ病、FABP5,3と機能性精神障害(統合失調症および躁うつ病)との遺伝解析,2.FABP5,3の機能性精神障害死後脳における遺伝子発現解析,3.Fabp7ノックアウトマウスの情動関連表現型の解析,4.ヒト末梢血におけるFABP7,5,3の遺伝子発現レベルの解析(正常群、未服薬の統合失調症群および気分障害群),5.胎児期マウスに種々の不飽和脂肪酸含量食餌を与えたとき、成体脳でのFabp7,5,3の発現解析および行動解析。1.については、FABP7と躁うつ病の関連は認めたが、FABP5は遺伝解析に使える多型が存在せず解析が不可能であった。FABP3はどちらの疾患にも関連していなかった。2.については、FABP5は脳発達期に多く発現し、両疾患の死後脳で発現が上昇していた。 これは脳発達期の脂肪酸代謝の代償的変化と推察される。一方、FABP3は成体脳での発現が多く、死後脳でも発現変化がなかった。3.いろいろなテストバッテリーのうち、オープンフィールドテストで中央領域にいる時間が短く、不安の亢進が示唆された。4。末梢血ではFABP5 mRNAのみ測定可能であった。死後脳とは逆に、統合失調症群および気分障害群で発現低下が認められた。これも持続的な脂肪酸代謝の異常を反映しているものと判断された。5.発現解析では、不飽和脂肪酸欠乏食を食べさせたマウス脳で、ヒト精神疾患死後脳と同様Fabp7,5の発現上昇が認められた。行動上ははっきりした異常は見られなかったが、覚醒剤に対する反応性が亢進しており、ヒトのARMS(At Risk Mental State)の状態と考えられ、興味深いと思われる

  18. Role of polyunsaturated fatty acids in the development of schizophrenia Competitive

    MAEKAWA Motoko

    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: The Institute of Physical and Chemical Research

    2009 - 2010

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    In mice fed polyunsaturated fatty acids (PUFAs)-deficient diet during the brain developmental stage, we observed broad downregulation of genes related to oligodendrocyte and GABAergic systems, which is a current theory of functional psychoses. Moreover, we revealed that 1) mice raised with PUFAs-deficient diet showed poor volition detected by Y maze test, 2) neuronal activity of such mice was altered, which was examined by Mn-enhanced MRI. These results provide innovative clues for the pathophysiology of mental disorders, demonstrating an important role of PUFAs during neurodevelopement.

  19. 遺伝子改変マウスを用いた情動記憶消去の分子神経機構の解明

    湯浅 茂樹, 服部 功太郎, 加藤 怜子, 前川 素子, 相馬 美歩

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特定領域研究

    Category: 特定領域研究

    Institution: 国立精神・神経センター

    2006 - 2007

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    Fynチロシンキナーゼは大脳辺縁系に強く発現し,その遺伝子欠損マウスは情動行動異常を示す。本研究ではFyn欠損マウスを情動記憶障害モデルとして,本分子の欠損によって引き起こされる細胞内情報伝達過程の異常と恐怖情動記憶の形成・消去の障害との関連性を解析する。このために,まずFynが情動記憶の形成と消去に関連してどのように変動し,Fyn依存性の蛋白質チロシンリン酸化シグナル伝達系の変動とどのように相関するかを解析し,これらのシステムが恐怖記憶に関連する神経回路を制御する分子神経機構について検討する。 結果と考察 1.野生型マウスでは文脈的恐怖条件付けにおける記憶獲得過程において,背側海馬においてFynの一過性の活性化がおこることを明らかにした。この活性化は条件刺激と無条件刺激の連合に依存していた。また,Fyn欠損マウスの文脈的恐怖条件付けにおいては,異なった文脈の弁別が特異的に障害されていることが明らかになった。一方,野生型の手がかり的恐怖条件付けにおいては扁桃体でFynの活性化がおこることが明らかになった。 2.海馬ならびに扁桃体においてFynの活性化に続いてNMDA受容体NR2Bサブユニットのチロシンリン酸化の亢進が認められた。 3.恐怖記憶の消去過程では扁桃体の活性化型FynとNR2Bリン酸化は共に低下した。一方,sulpirideによる恐怖記憶の消去促進に対応して扁桃体外側核におけるc-Fos発現が亢進した。 4.以上の結果から,Fynの活性化は恐怖記憶の獲得時に亢進し,消去過程では低下すること,Fyn下流の蛋白質チロシンリン酸化も恐怖記憶獲得時には亢進し,消去過程では低下することが明らかになった。Fyn欠損マウスでは恐怖記憶形成の亢進,消去過程の障害が認められ,逆にFynの過剰発現マウスでは情動記憶形成の低下が認められることから,Fynは下流蛋白質のチロシンリン酸化を介して過度の記憶形成を抑えることが推測される。また,野生型マウスの恐怖記憶消去過程ではリン酸化チロシンの脱リン酸化が促進されると考えられ,記憶形成過程とは異なったシグナル伝達経路が関与する可能性がある。

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