研究者詳細

顔写真

ユ　シゼン
兪　志前
Zhiqian Yu
所属
大学院医学系研究科　医科学専攻　神経・感覚器病態学講座（精神神経学分野）
職名
講師
学位

  • 博士（歯学）（東北大学）

プロフィール
神経免疫学を用いて、双極性障害、心的外傷後ストレス障害の病態解明を行っています。

経歴 1

  • 2021年4月 ～ 継続中
    東北大学・医学系研究科・精神神経学分野・講師

研究キーワード 1

  • 包括脳ネットワーク

研究分野 1

  • ライフサイエンス / 神経科学一般 / 気分安定薬

受賞 4

  1. JSBP 33h Annual Conference Award for the Excellent Poster

    2011年5月

  2. JSNP Excellent Presentation Award for CINP 2010

    2010年9月

  3. Tohoku University President's Award

    2006年3月

  4. Tohoku University Professor Fujino Award

    2006年3月

論文 69

  1. Effects of pharmacological inhibition of FABP4 during gestation and lactation on offspring neurodevelopment and behavior. 国際誌 査読有り

    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年3月14日

    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. Experimenters' sex modulates anxiety-like behavior, contextual fear, and microglial oxytocin transcription in mice 査読有り

    Mai Sakai, Zhiqian Yu, Rosanne Picotin, Tomoko Kasahara, Yoshie Kikuchi, Chiaki Ono, Mizuki Hino, Yasuto Kunii, Yuko Maejima, Kenju Shimomura, Miharu Nakanishi, Takaaki Abe, Hatsumi Yoshii, Hiroaki Tomita

    Behavioural Brain Research　115480-115480　2025年2月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.bbr.2025.115480 　

    ISSN：0166-4328

  3. Identification of risk loci for postpartum depression in a genome-wide association study. 国際誌 査読有り

    Xue Li, Nagahide Takahashi, Akira Narita, Yukako Nakamura, Mika Sakurai-Yageta, Keiko Murakami, Mami Ishikuro, Taku Obara, Masahiro Kikuya, Fumihiko Ueno, Hirohito Metoki, Hisashi Ohseto, Ippei Takahashi, Tomohiro Nakamura, Noriko Warita, Tomoka Shoji, Zhiqian Yu, Chiaki Ono, Natsuko Kobayashi, Saya Kikuchi, Tasuku Matsuki, Fuji Nagami, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Norio Ozaki, Gen Tamiya, Shinichi Kuriyama, Hiroaki Tomita

    Psychiatry and clinical neurosciences　78　(11)　712-720　2024年11月

    DOI： 10.1111/pcn.13731 　

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    AIM: Genome-wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD-associated loci. METHODS: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders. RESULTS: A meta-analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10-8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over-represented in categories including long-term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling. CONCLUSION: The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis.

  4. Glial Markers of Suicidal Behavior in the Human Brain-A Systematic Review of Postmortem Studies. 国際誌 査読有り

    Mana Yamamoto, Mai Sakai, Zhiqian Yu, Miharu Nakanishi, Hatsumi Yoshii

    International journal of molecular sciences　25　(11)　2024年5月25日

    DOI： 10.3390/ijms25115750 　

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    Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study aimed to identify and synthesize evidence of the relationship between glial dysfunction and suicidal behavior to understand the neurobiology of suicide. As of 26 January 2024, 46 articles that met the inclusion criteria were identified by searching PubMed and ISI Web of Science. Most postmortem studies, including 30 brain regions, have determined no density or number of total Nissl-glial cell changes in suicidal patients with major psychiatric disorders. There were 17 astrocytic, 14 microglial, and 9 oligodendroglial studies using specific markers of each glial cell and further on their specific gene expression. Those studies suggest that astrocytic and oligodendroglial cells lost but activated microglia in suicides with affective disorder, bipolar disorders, major depression disorders, or schizophrenia in comparison with non-suicided patients and non-psychiatric controls. Although the data from previous studies remain complex and cannot fully explain the effects of glial cell dysfunction related to suicidal behaviors, they provide risk directions potentially leading to suicide prevention.

  5. Response to ‘Potential role of anti‐inflammatory cytokines in postpartum depression: Considerations for future research and improvement’ 査読有り

    Chiaki T. Ono, Zhiqian Yu, Saya Kikuchi, Natsuko Kobayashi, Hiroaki Tomita

    Psychiatry and Clinical Neurosciences　78　(5)　335-336　2024年3月20日

    出版者・発行元： Wiley

    DOI： 10.1111/pcn.13660 　

    ISSN：1323-1316

    eISSN：1440-1819

  6. 統合失調症と性差〜なぜ男性の病理は重いのか.

    兪志前, 小松浩, 富田博秋

    精神医学　66　(1)　81-87　2024年1月

  7. AI を用いたうつ病の病態解明と個別化精神医療に向けた展望.

    富田 博秋, 兪 志前, 李 雪, 高橋 雄太

    臨床精神薬理　26　(3)　285-292　2023年11月

  8. The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain 査読有り

    Kazusa Miyahara, Mizuki Hino, Zhiqian Yu, Chiaki Ono, Atsuko Nagaoka, Masataka Hatano, Risa Shishido, Hirooki Yabe, Hiroaki Tomita, Yasuto Kunii

    Frontiers in Psychiatry　14　2023年7月14日

    出版者・発行元： Frontiers Media SA

    DOI： 10.3389/fpsyt.2023.1156524 　

    eISSN：1664-0640

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    Background Evaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples. Methods We isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis. Results We identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing. Conclusion The current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.

  9. Comprehensive evaluation of machine learning algorithms for predicting sleep–wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability 査読有り

    Xue Li, Chiaki Ono, Noriko Warita, Tomoka Shoji, Takashi Nakagawa, Hitomi Usukura, Zhiqian Yu, Yuta Takahashi, Kei Ichiji, Norihiro Sugita, Natsuko Kobayashi, Saya Kikuchi, Ryoko Kimura, Yumiko Hamaie, Mizuki Hino, Yasuto Kunii, Keiko Murakami, Mami Ishikuro, Taku Obara, Tomohiro Nakamura, Fuji Nagami, Takako Takai, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Gen Tamiya, Nobuo Fuse, Susumu Fujii, Masaharu Nakayama, Shinichi Kuriyama, Masayuki Yamamoto, Nobuo Yaegashi, Noriyasu Homma, Hiroaki Tomita

    Frontiers in Psychiatry　14　2023年6月6日

    出版者・発行元： Frontiers Media SA

    DOI： 10.3389/fpsyt.2023.1104222 　

    eISSN：1664-0640

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    Introduction Perinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep–wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV). Methods Nine HRV indicators (features) and sleep–wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep–wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated—shallow sleep, deep sleep, and the two types of wake conditions—was also tested. Results and Discussion In the test for predicting three types of sleep–wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82–0.88) and accuracy (0.78–0.81). The test using four types of sleep–wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep–wake conditions. Among the seven features, “the number of interval differences of successive RR intervals greater than 50 ms (NN50)” and “the proportion dividing NN50 by the total number of RR intervals (pNN50)” were useful to predict sleep–wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

  10. Association between low levels of anti-inflammatory cytokines during pregnancy and postpartum depression. 国際誌 査読有り

    Chiaki T Ono, Zhiqian Yu, Taku Obara, Mami Ishikuro, Keiko Murakami, Masahiro Kikuya, Saya Kikuchi, Natsuko Kobayashi, Hisaaki Kudo, Soichi Ogishima, Naoko Minegishi, Junichi Sugawara, Shinichi Kuriyama, Masayuki Yamamoto, Nobuo Yaegashi, Hiroaki Tomita

    Psychiatry and clinical neurosciences　77　(8)　434-441　2023年5月13日

    DOI： 10.1111/pcn.13566 　

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    AIM: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. METHODS: A nested, case-control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age-matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three-generation cohort. Concentrations of nine plasma cytokines (IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNF-α) in plasma collected at the time of enrollment during pregnancy and one month after delivery were determined using an immunoassay kit. RESULTS: Cross-sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL-4 levels during pregnancy and after delivery than the control group, and that plasma IL-4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL-10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL-10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN-γ, IL-6, IL-12p40, and TNF-α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. CONCLUSIONS AND RELEVANCE: These results suggest a potential protective effect of the anti-inflammatory cytokines IL-4 and IL-10 during pregnancy against the development of PPD. This article is protected by copyright. All rights reserved.

  11. N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-α Signaling 査読有り

    Mai Sakai, Zhiqian Yu, Masayuki Taniguchi, Rosanne Picotin, Nanami Oyama, David Stellwagen, Chiaki Ono, Yoshie Kikuchi, Ko Matsui, Miharu Nakanishi, Hatsumi Yoshii, Tomoyuki Furuyashiki, Takaaki Abe, Hiroaki Tomita

    International Journal of Molecular Sciences　24　(4)　3798-3798　2023年2月14日

    出版者・発行元： MDPI AG

    DOI： 10.3390/ijms24043798 　

    eISSN：1422-0067

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    N-acetylcysteine (NAC) is an antioxidant that prevents tumor necrosis factor (TNF)-α-induced cell death, but it also acts as a pro-oxidant, promoting reactive oxygen species independent apoptosis. Although there is plausible preclinical evidence for the use of NAC in the treatment of psychiatric disorders, deleterious side effects are still of concern. Microglia, key innate immune cells in the brain, play an important role in inflammation in psychiatric disorders. This study aimed to investigate the beneficial and deleterious effects of NAC on microglia and stress-induced behavior abnormalities in mice, and its association with microglial TNF-α and nitric oxide (NO) production. The microglial cell line MG6 was stimulated by Escherichia coli lipopolysaccharide (LPS) using NAC at varying concentrations for 24 h. NAC inhibited LPS-induced TNF-α and NO synthesis, whereas high concentrations (≥30 mM) caused MG6 mortality. Intraperitoneal injections of NAC did not ameliorate stress-induced behavioral abnormalities in mice, but high-doses induced microglial mortality. Furthermore, NAC-induced mortality was alleviated in microglial TNF-α-deficient mice and human primary M2 microglia. Our findings provide ample evidence for the use of NAC as a modulating agent of inflammation in the brain. The risk of side effects from NAC on TNF-α remains unclear and merits further mechanistic investigations.

  12. Decreased β‐hydroxybutyrate and ketogenic amino acid levels in depressed human adults 査読有り

    Shiho Sato, Zhiqian Yu, Mai Sakai, Ikuko N. Motoike, Daisuke Saigusa, Ryo Hirayama, Yoshie Kikuchi, Takaaki Abe, Kengo Kinoshita, Seizo Koshiba, Hiroaki Tomita

    European Journal of Neuroscience　2023年2月7日

    出版者・発行元： Wiley

    DOI： 10.1111/ejn.15931 　

    ISSN：0953-816X

    eISSN：1460-9568

  13. Microarray dataset of gene transcription in mouse microglia and peripheral monocytes in contextual fear conditioning 査読有り

    Zhiqian Yu, Mai Sakai, Hotaka Fukushima, Chiaki Ono, Yoshie Kikuchi, Ryuta Koyama, Ko Matsui, Tomoyuki Furuyashiki, Satoshi Kida, Hiroaki Tomita

    Data in Brief　46　108862-108862　2023年2月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.dib.2022.108862 　

    ISSN：2352-3409

  14. Plasma metabolic disturbances during pregnancy and postpartum in women with depression. 国際誌 査読有り

    Zhiqian Yu, Naomi Matsukawa, Daisuke Saigusa, Ikuko N Motoike, Chiaki Ono, Yasunobu Okamura, Tomomi Onuma, Yuta Takahashi, Mai Sakai, Hisaaki Kudo, Taku Obara, Keiko Murakami, Matusyuki Shirota, Saya Kikuchi, Natsuko Kobayashi, Yoshie Kikuchi, Junichi Sugawara, Naoko Minegishi, Soichi Ogishima, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Shinichi Kuriyama, Seizo Koshiba, Hiroaki Tomita

    iScience　25　(12)　105666-105666　2022年12月22日

    DOI： 10.1016/j.isci.2022.105666 　

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    Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

  15. Sex-Specific Differences in the Transcriptome of the Human Dorsolateral Prefrontal Cortex in Schizophrenia. 国際誌 査読有り

    Zhiqian Yu, Kazuko Ueno, Ryo Funayama, Mai Sakai, Naoki Nariai, Kaname Kojima, Yoshie Kikuchi, Xue Li, Chiaki Ono, Junpei Kanatani, Jiro Ono, Kazuya Iwamoto, Kenji Hashimoto, Kengo Kinoshita, Keiko Nakayama, Masao Nagasaki, Hiroaki Tomita

    Molecular neurobiology　60　(2)　1083-1098　2022年11月22日

    DOI： 10.1007/s12035-022-03109-6 　

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    Schizophrenia presents clinical and biological differences between males and females. This study investigated transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) using postmortem data from the largest RNA-sequencing (RNA-seq) database on schizophrenic cases and controls. Data for 154 male and 113 female controls and 160 male and 93 female schizophrenic cases were obtained from the CommonMind Consortium. In the RNA-seq database, the principal component analysis showed that sex effects were small in schizophrenia. After we analyzed the impact of sex-specific differences on gene expression, the female group showed more significantly changed genes compared with the male group. Based on the gene ontology analysis, the female sex-specific genes that changed were overrepresented in the mitochondrion, ATP (phosphocreatine and adenosine triphosphate)-, and metal ion-binding relevant biological processes. An ingenuity pathway analysis revealed that the differentially expressed genes related to schizophrenia in the female group were involved in midbrain dopaminergic and γ-aminobutyric acid (GABA)-ergic neurons and microglia. We used methylated DNA-binding domain-sequencing analyses and microarray to investigate the DNA methylation that potentially impacts the sex differences in gene transcription using a maternal immune activation (MIA) murine model. Among the sex-specific positional genes related to schizophrenia in the PFC of female offspring from MIA, the changes in the methylation and transcriptional expression of loci ACSBG1 were validated in the females with schizophrenia in independent postmortem samples by real-time PCR and pyrosequencing. Our results reveal potential genetic risks in the DLPFC for the sex-dependent prevalence and symptomology of schizophrenia.

  16. Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia. 国際誌 査読有り

    Zhiqian Yu, Mai Sakai, Hotaka Fukushima, Chiaki Ono, Yoshie Kikuchi, Ryuta Koyama, Ko Matsui, Tomoyuki Furuyashiki, Satoshi Kida, Hiroaki Tomita

    Brain research bulletin　189　57-68　2022年8月17日

    DOI： 10.1016/j.brainresbull.2022.08.017 　

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    Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning.

  17. Identification of oxytocin expression in human and murine microglia. 国際誌 査読有り

    Yuko Maejima, Shoko Yokota, Tomoyuki Ono, Zhiqian Yu, Megumi Yamachi, Shizu Hidema, Kenneth E Nollet, Katsuhiko Nishimori, Hiroaki Tomita, Hiroyuki Yaginuma, Kenju Shimomura

    Progress in neuro-psychopharmacology & biological psychiatry　119　110600-110600　2022年7月13日

    DOI： 10.1016/j.pnpbp.2022.110600 　

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    BACKGROUND: Oxytocin is a neuropeptide synthesized in the hypothalamus. In addition to its role in parturition and lactation, oxytocin mediates social behavior and pair bonding. The possibility of using oxytocin to modify behavior in neurodevelopmental disorders, such as autism spectrum disorder, is of clinical interest. Microglia are tissue-resident macrophages with roles in neurogenesis, synapse pruning, and immunological mediation of brain homeostasis. Recently, oxytocin was found to attenuate microglial secretion of proinflammatory cytokines, but the source of this oxytocin was not established. This prompted us to investigate whether microglia themselves were the source. METHODS: We examined oxytocin expression in human and murine brain tissue in both sexes using immunohistochemistry. Oxytocin mRNA expression and secretion were examined in isolated murine microglia from wild type and oxytocin-knockout mice. Also, secretion of oxytocin and cytokines was measured in cultured microglia (MG6) stimulated with lipopolysaccharide (LPS). RESULTS: We identified oxytocin expression in microglia of human brain tissue, cultured microglia (MG6), and primary murine microglia. Furthermore, LPS stimulation increased oxytocin mRNA expression in primary murine microglia and MG6 cells, and oxytocin secretion as well. A positive correlation between oxytocin and IL-1β, IL-10 secretion emerged, respectively. CONCLUSION: This may be the first demonstration of oxytocin expression in microglia. Functionally, oxytocin might regulate inflammatory cytokine release from microglia in a paracrine/autocrine manner.

  18. Surface translocation of Kir2.1 channel induces IL-1β secretion in microglia. 国際誌 査読有り

    Yuko Maejima, Shoichiro Horita, Shoko Yokota, Megumi Yamachi, Masaru Shimizu, Tomoyuki Ono, Zhiqian Yu, Hiroaki Tomita, Kenju Shimomura

    Molecular and cellular neurosciences　120　103734-103734　2022年5月

    DOI： 10.1016/j.mcn.2022.103734 　

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    One of the major properties of microglia is to secrete cytokines as a reaction to stress such as lipopolysaccharide (LPS) application. The mechanism of cytokine secretion from the microglia upon stress through the inflammasome-mediated release process is well studied, and the voltage-gated Kv1.3 channel is known to play an important role in this process. Most previous studies investigated long-term inflammasome-mediated cytokine release (at least over 4 h) and there are only a few studies on the acute reaction (within minutes order) of the microglia to stress and its cytokine secretion capacity. In this study, we found that LPS induced an increase in Kir2.1 current within 15 min after administration but had no effect on voltage-dependent outward currents. Moreover, cytological and western blot analysis revealed that the increase in the Kir2.1 channel current after LPS administration was induced by the translocation of Kir2.1 from the cytoplasm to the cell surface. From an experiment using the inhibitor and trafficking mutation of Kir2.1, an increase in Kir2.1 was found to contribute to the secretion of the inflammatory cytokine, IL-1β. Although the physiological significance of this acute IL-1β secretion remains unclear, our present data imply that Kir2.1 translocation functions as a regulator of IL-1β secretion, and therefore becomes a potential target to control cytokine release from microglia.

  19. Depression and anxiety among nursing students during the COVID-19 pandemic in Tohoku region, Japan: A cross-sectional survey. 査読有り

    Mai Sakai, Miharu Nakanishi, Zhiqian Yu, Gen Takagi, Keita Toshi, Koubun Wakashima, Hatsumi Yoshii

    Japan journal of nursing science : JJNS　19　(3)　e12483　2022年4月5日

    DOI： 10.1111/jjns.12483 　

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    AIM: Restrictions such as physical distancing and online learning for college students were implemented due to the COVID-19 pandemic. Owing to this, students may experience psychological distress from social isolation and loneliness. Nursing students are subjected to an exacerbated level of distress during the pandemic due to their role as health professionals. Therefore, the present study aimed to investigate the level of anxiety and depression among Japanese nursing students, according to their perceived vulnerability to COVID-19. METHODS: A total of 281 college students (104 nursing students and 177 other college students) responded to a web-based anonymous questionnaire survey from 18 August to 31 October 2020. The Hospital Anxiety and Depression Scale was used to evaluate anxiety (HADS-A) and depression (HADS-D). Perceived vulnerability to COVID-19 was assessed using the Perceived Vulnerability to Disease Scale. RESULTS: In both groups of students, the prevalence of both anxiety (30.5% in nursing students; 69.5% in others) and depressive symptoms (31.1% in nursing students; 68.9% in others) were remarkably high. There were no significant differences in anxiety and depression between nursing and other students after adjusting for perceived vulnerability to COVID-19 plus socio-demographic characteristics and stress coping styles. Perceived vulnerability and its interactions with nursing did not show a significant association with either depression or anxiety. CONCLUSION: This study highlights the need for greater support and preventive strategies for mental health problems for college students during the COVID-19 pandemic regardless of perceived vulnerability.

  20. A psychiatric disorder risk polymorphism of ITIH3 is associated with multiple neuroimaging phenotypes in young healthy adults. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono Tanaka, Zhiqian Yu, Izumi Matsudaira, Rui Nouchi, Tadashi Imanishi, Ryuta Kawashima

    Psychiatry and clinical neurosciences　76　(6)　271-273　2022年3月8日

    DOI： 10.1111/pcn.13347 　

  21. Deficient Autophagy in Microglia Aggravates Repeated Social Defeat Stress-Induced Social Avoidance. 国際誌 査読有り

    Mai Sakai, Zhiqian Yu, Ryo Hirayama, Masa Nakasato, Yoshie Kikuchi, Chiaki Ono, Hiroshi Komatsu, Miharu Nakanishi, Hatsumi Yoshii, David Stellwagen, Tomoyuki Furuyashiki, Masaaki Komatsu, Hiroaki Tomita

    Neural plasticity　2022　7503553-7503553　2022年

    DOI： 10.1155/2022/7503553 　

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    Major depressive disorder (MDD) is associated with repeated exposure to environmental stress. Autophagy is activated under various stress conditions that are associated with several diseases in the brain. This study was aimed at elucidating the autophagy signaling changes in the prefrontal cortex (PFC) under repeated social defeat (RSD) to investigate the involvement of microglial autophagy in RSD-induced behavioral changes. We found that RSD stress, an animal model of MDD, significantly induced initial autophagic signals followed by increased transcription of autophagy-related genes (Atg6, Atg7, and Atg12) in the PFC. Similarly, significantly increased transcripts of ATGs (Atg6, Atg7, Atg12, and Atg5) were confirmed in the postmortem PFC of patients with MDD. The protein levels of the prefrontal cortical LC3B were significantly increased, whereas p62 was significantly decreased in the resilient but not in susceptible mice and patients with MDD. This indicates that enhanced autophagic flux may alleviate stress-induced depression. Furthermore, we identified that FKBP5, an early-stage autophagy regulator, was significantly increased in the PFC of resilient mice at the transcript and protein levels. In addition, the resilient mice exhibited enhanced autophagic flux in the prefrontal cortical microglia, and the autophagic deficiency in microglia aggravated RSD-induced social avoidance, indicating that microglial autophagy involves stress-induced behavioral changes.

  22. Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex. 国際誌 査読有り

    Hikaru Takeuchi, Ryosuke Kimura, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Izumi Matsudaira, Rui Nouchi, Ryoichi Yokoyama, Yuka Kotozaki, Seishu Nakagawa, Sugiko Hanawa, Kunio Iizuka, Atsushi Sekiguchi, Tsuyoshi Araki, Carlos Makoto Miyauchi, Shigeyuki Ikeda, Kohei Sakaki, Kelssy H Dos S Kawata, Takayuki Nozawa, Susumu Yokota, Daniele Magistro, Tadashi Imanishi, Ryuta Kawashima

    Human brain mapping　42　(18)　6028-6037　2021年9月29日

    DOI： 10.1002/hbm.25667 　

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    It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

  23. Tumor necrosis factor α negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory. 国際誌 査読有り

    Shohei Takahashi, Hotaka Fukushima, Zhiqian Yu, Hiroaki Tomita, Satoshi Kida

    Brain, behavior, and immunity　94　79-88　2021年5月

    DOI： 10.1016/j.bbi.2021.02.033 　

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    Neural inflammation is associated with cognitive decline, especially learning and memory. Tumor necrosis factor α (TNFα) is a major cytokine generated during neuroinflammation. Previous studies indicated that TNFα impairs hippocampus-dependent memory including contextual fear and spatial memories. However, it is unknown which memory processes are impaired by TNFα. Here, we show that TNFα blocked the retrieval and reconsolidation of contextual fear and spatial memories. Micro-infusion of TNFα into the dorsal hippocampus at 6-18 h before retrieval impaired the retrieval of contextual fear memory, although micro-infusion before contextual fear conditioning had no effect on memory formation. Interestingly, hippocampal TNFα micro-infusion before memory retrieval decreased freezing responses, even at 24 h after retrieval, suggesting that TNFα impairs the reconsolidation of contextual fear memory. Similarly, hippocampal TNFα micro-infusion impaired the retrieval and reconsolidation of spatial memory in the Morris water maze. Consistent with these observations, hippocampal TNFα micro-infusion before retrieval blocked the induction of c-fos expression in the hippocampus, which is a marker of neural activation, in response to the retrieval of contextual fear memory. Collectively, our findings indicate that TNFα negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

  24. Association Between OLIG2 Gene SNP rs1059004 and Negative Self-Schema Constructing Trait Factors Underlying Susceptibility to Depression 査読有り

    Hiroshi Komatsu, Hikaru Takeuchi, Chiaki Ono, Zhiqian Yu, Yoshie Kikuchi, Yoshihisa Kakuto, Shunichi Funakoshi, Takashi Ono, Ryuta Kawashima, Yasuyuki Taki, Hiroaki Tomita

    Frontiers in Psychiatry　12　2021年3月8日

    出版者・発行元： Frontiers Media SA

    DOI： 10.3389/fpsyt.2021.631475 　

    eISSN：1664-0640

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    Recent evidence has indicated that the disruption of oligodendrocytes may be involved in the pathogenesis of depression. Genetic factors are likely to affect trait factors, such as characteristics, rather than state factors, such as depressive symptoms. Previously, a negative self-schema had been proposed as the major characteristic of constructing trait factors underlying susceptibility to depression. Thus, the association between a negative self-schema and the functional single nucleotide polymorphism (SNP) rs1059004 in the <italic>OLIG2</italic> gene, which influences <italic>OLIG2</italic> gene expression, white matter integrity, and cerebral blood flow, was evaluated. A total of 546 healthy subjects were subjected to genotype and psychological evaluation using the Beck Depression Inventory-II (BDI-II) and the Brief Core Schema Scale (BCSS). The rs1059004 SNP was found to be associated with the self-schema subscales of the BCSS and scores on the BDI-II in an allele dose-dependent manner, and to have a predictive impact on depressive symptoms via a negative-self schema. The results suggest the involvement of a genetic factor regulating oligodendrocyte function in generating a negative-self schema as a trait factor underlying susceptibility to depression.

  25. Heart Rate Information-Based Machine Learning Prediction of Emotions Among Pregnant Women. 国際誌 査読有り

    Xue Li, Chiaki Ono, Noriko Warita, Tomoka Shoji, Takashi Nakagawa, Hitomi Usukura, Zhiqian Yu, Yuta Takahashi, Kei Ichiji, Norihiro Sugita, Natsuko Kobayashi, Saya Kikuchi, Yasuto Kunii, Keiko Murakami, Mami Ishikuro, Taku Obara, Tomohiro Nakamura, Fuji Nagami, Takako Takai, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Gen Tamiya, Nobuo Fuse, Shinichi Kuriyama, Masayuki Yamamoto, Nobuo Yaegashi, Noriyasu Homma, Hiroaki Tomita

    Frontiers in psychiatry　12　799029-799029　2021年

    DOI： 10.3389/fpsyt.2021.799029 　

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    In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including "happy," as a positive emotion and "anxiety," "sad," "frustrated," as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions.

  26. Machine learning to reveal hidden risk combinations for the trajectory of posttraumatic stress disorder symptoms 査読有り

    Yuta Takahashi, Kazuki Yoshizoe, Masao Ueki, Gen Tamiya, Zhiqian Yu, Yusuke Utsumi, Atsushi Sakuma, Koji Tsuda, Atsushi Hozawa, Ichiro Tsuji, Hiroaki Tomita

    Scientific Reports　10　(1)　2020年12月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s41598-020-78966-z 　

    eISSN：2045-2322

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    <title>Abstract</title>The nature of the recovery process of posttraumatic stress disorder (PTSD) symptoms is multifactorial. The Massive Parallel Limitless-Arity Multiple-testing Procedure (MP-LAMP), which was developed to detect significant combinational risk factors comprehensively, was utilized to reveal hidden combinational risk factors to explain the long-term trajectory of the PTSD symptoms. In 624 population-based subjects severely affected by the Great East Japan Earthquake, 61 potential risk factors encompassing sociodemographics, lifestyle, and traumatic experiences were analyzed by MP-LAMP regarding combinational associations with the trajectory of PTSD symptoms, as evaluated by the Impact of Event Scale-Revised score after eight years adjusted by the baseline score. The comprehensive combinational analysis detected 56 significant combinational risk factors, including 15 independent variables, although the conventional bivariate analysis between single risk factors and the trajectory detected no significant risk factors. The strongest association was observed with the combination of short resting time, short walking time, unemployment, and evacuation without preparation (adjusted <italic>P</italic> value = 2.2 × 10−4, and raw <italic>P</italic> value = 3.1 × 10−9). Although short resting time had no association with the poor trajectory, it had a significant interaction with short walking time (<italic>P</italic> value = 1.2 × 10−3), which was further strengthened by the other two components (<italic>P</italic> value = 9.7 × 10−5). Likewise, components that were not associated with a poor trajectory in bivariate analysis were included in every observed significant risk combination due to their interactions with other components. Comprehensive combination detection by MP-LAMP is essential for explaining multifactorial psychiatric symptoms by revealing the hidden combinations of risk factors.

  27. Sex-Dependent Effects of the APOE ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Ryan Browne, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Rui Nouchi, Ryoichi Yokoyama, Yuka Kotozaki, Seishu Nakagawa, Atsushi Sekiguchi, Kunio Iizuka, Sugiko Hanawa, Tsuyoshi Araki, Carlos Makoto Miyauchi, Kohei Sakaki, Takayuki Nozawa, Shigeyuki Ikeda, Susumu Yokota, Daniele Magistro, Yuko Sassa, Ryuta Kawashima

    Cerebral Cortex　31　(1)　672-680　2020年9月21日

    出版者・発行元： Oxford University Press (OUP)

    DOI： 10.1093/cercor/bhaa251 　

    ISSN：1047-3211

    eISSN：1460-2199

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    <title>Abstract</title> The APOE ɛ4 allele is associated with a risk of Alzheimer’s disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex–genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex–genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females.

  28. Effect of the interaction between BDNF Val66Met polymorphism and daily physical activity on mean diffusivity. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Atsushi Sekiguchi, Rui Nouchi, Yuka Kotozaki, Seishu Nakagawa, Carlos Makoto Miyauchi, Kunio Iizuka, Ryoichi Yokoyama, Takamitsu Shinada, Yuki Yamamoto, Sugiko Hanawa, Tsuyoshi Araki, Keiko Kunitoki, Yuko Sassa, Ryuta Kawashima

    Brain imaging and behavior　14　(3)　806-820　2020年6月

    DOI： 10.1007/s11682-018-0025-8 　

    ISSN：1931-7557

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    Numerous studies have reported that the Met allele of the brain-derived neurotrophic factor (BDNF) gene polymorphism reduces neural plasticity. A reduction in mean diffusivity (MD) in diffusion tensor imaging (DTI) characteristically reflects the neural plasticity that involves increased tissue components. In this study, we revealed that the number of Met-BDNF alleles was negatively associated with MD throughout the whole-brain gray and white matter areas of 743 subjects using DTI and whole-brain multiple regression analyses. Within the same sample, the region of interest analysis revealed that the number of Met-BDNF alleles significantly and positively correlated with the mean FA value in the body of the corpus callosum. In addition, we observed interaction effects between BDNF Val66Met polymorphism and daily physical activity levels on MD, but not FA, in significant clusters of the bilateral hemisphere (n = 577 subjects). Post-hoc multiple regression analyses revealed that after correcting for confounding variables, there was a significant negative correlation between the physical activity level and mean MD of the whole brain in the Val/Val group [standardized partial regression coefficient (β) = -0.196, P = 0.005, t = -2.825], but not in the Val/Met (β = 0.050, P = 0.412, t = 0.822) and Met/Met groups (β = 0.092, P = 0.382, t = 0.878). These results underscore the importance of the interaction between physical activity and the BDNF Val66Met polymorphism, which affects the plasticity of neural mechanisms.

  29. Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity 査読有り

    Hiroshi Komatsu, Hikaru Takeuchi, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Kunio Iizuka, Yuji Takano, Yoshihisa Kakuto, Shunichi Funakoshi, Takashi Ono, Junko Ito, Yasuto Kunii, Mizuki Hino, Atsuko Nagaoka, Yasushi Iwasaki, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Hirotsugu Azechi, Noriko Kudo, Ryota Hashimoto, Hirooki Yabe, Mari Yoshida, Yuko Saito, Akiyoshi Kakita, Nobuo Fuse, Ryuta Kawashima, Yasuyuki Taki, Hiroaki Tomita

    Schizophrenia Bulletin　in press　2020年

  30. 骨吸収抑制薬bisphosphonatesによる顎骨壊死の機序・予防・治療に関する基礎研究

    遠藤 康男, 船山 ひろみ, 山口 晃史, 門馬 祐子, 兪 志前, 鄧 雪, 大泉 丈史, 四釜 洋介, 田中 志典, 岡田 諭, 金 始瑛, 木山 朋美, 坂東 加南, 島 和弘, 鈴木 飛佳理, 高橋 哲

    薬学雑誌　140　(1)　63-79　2020年1月

    出版者・発行元： (公社)日本薬学会

    ISSN：0031-6903

    eISSN：1347-5231

  31. A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Rui Nouchi, Ryoichi Yokoyama, Yuka Kotozaki, Seishu Nakagawa, Atsushi Sekiguchi, Kunio Iizuka, Sugiko Hanawa, Tsuyoshi Araki, Carlos Makoto Miyauchi, Kohei Sakaki, Takayuki Nozawa, Shigeyuki Ikeda, Susumu Yokota, Daniele Magistro, Yuko Sassa, Ryuta Kawashima

    Cerebral cortex (New York, N.Y. : 1991)　29　(8)　3211-3219　2019年7月22日

    DOI： 10.1093/cercor/bhy189 　

    ISSN：1047-3211

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    Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women. Here we investigated the sex-specific effects of the CACNA1C variant rs1024582 on psychiatry-related traits, brain activity during tasks and rest, and brain volume in 1207 normal male and female subjects. After correcting for multiple comparisons, there were significant interaction effects between sex and the minor allele of this polymorphism on the hostile behavior subscale scores of the Coronary-Prone Type Scale mediated by higher scores in female carriers of the minor allele. Imaging analyses revealed significant interaction effects between sex and the minor allele on fractional amplitude of low-frequency fluctuations in the right dorsolateral prefrontal cortex and on brain activity during the 2-back task in areas of the right posterior cingulate cortex, right thalamus, and right hippocampus, which were all mediated by reduced activity in female carriers of the minor allele. Our results demonstrated that the rs1024582 risk variant of CACNA1C is associated with reduced activity in the frontolimbic regions at rest and during a working memory task as well as with greater hostility in females in the healthy population.

  32. OLIG2遺伝子多型(rs1059004)と自己スキーマ及び抑うつ症状との関連 査読有り

    小松 浩, 竹内 光, 菊地 淑恵, 小野 千晶, 兪 志前, 飯塚 邦夫, 角藤 芳久, 舩越 俊一, 大野 高志, 川島 隆太, 瀧 龍之, 富田 博秋

    精神神経学雑誌　(2019特別号)　S452-S452　2019年6月

    出版者・発行元： (公社)日本精神神経学会

    ISSN：0033-2658

  33. A minimal amount of tissue-based pH measurement to improve quality control in neuropsychiatric postmortem brain studies. 査読有り

    Chiaki T Ono, Zhiqian Yu, Yoshie Kikuchi, Yasuto Kunii, Mizuki Hino, Junya Matsumoto, Atsuko Nagaoka, Junko Ito, Yasushi Iwasaki, Hideo Hagihara, Tsuyoshi Miyakawa, Mari Yoshida, Yuko Saito, Shin-Ichi Niwa, Hirooki Yabe, Akiyoshi Kakita, Hiroaki Tomita

    Psychiatry and clinical neurosciences　73　(9)　566-573　2019年5月

    DOI： 10.1111/pcn.12863 　

    ISSN：1323-1316

    eISSN：1440-1819

  34. 東日本大震災による津波避難訓練の有効性

    中谷直樹, 根本晴美, YI Carine J, 佐藤文子, 新宮古都美, 庄子朋香, 佐藤翔輔, 土屋菜歩, 中村智洋, 成田暁, 小暮真奈, 菅原由美, 兪志前, GUNAWANSA Nicole, 栗山進一, 村尾修, 佐藤健, 今村文彦, 富田博秋

    宮城県公衆衛生学会会誌　(51)　12　2019年3月

    ISSN：0912-747X

  35. A single nucleotide polymorphism (-250 A/C) of the GFAP gene is associated with brain structures and cerebral blood flow 査読有り

    Yuta Takahashi, Hikaru Takeuchi, Mai Sakai, Zhiqian Yu, Yoshie Kikuchi, Fumiaki Ito, Hiroo Matsuoka, Osamu Tanabe, Jun Yasuda, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Tomita

    Psychiatry and Clinical Neurosciences　in press　2019年

  36. Dynamics of Platelet Behaviors as Defenders and Guardians: Accumulations in Liver, Lung, and Spleen in Mice. 査読有り

    Zhiqian Yu, Masahiro Shibazaki, Hirotada Otsuka, Haruhiko Takada, Masanori Nakamura, Yasuo Endo

    Biological & pharmaceutical bulletin　42　(8)　1253-1267　2019年

    DOI： 10.1248/bpb.b18-00975 　

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    Systemic platelet behaviors in experimental animals are often assessed by infusion of isotope-labeled platelets and measuring them under anesthesia. However, such procedures alter, therefore may not reveal, real-life platelet behaviors. 5-Hydroxytryptamine (5HT or serotonin) is present within limited cell-types, including platelets. In our studies, by measuring 5HT as a platelet-marker in non-anesthetized mice, we identified stimulation- and time-dependent accumulations in liver, lung, and/or spleen as important systemic platelet behaviors. For example, intravenous, intraperitoneal, or intragingival injection of lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria), interleukin (IL)-1, or tumor necrosis factor (TNF)-α induced hepatic platelet accumulation (HPA) and platelet translocation into the sinusoidal and perisinusoidal spaces or hepatocytes themselves. These events occurred "within a few hours" of the injection, caused hypoglycemia, and exhibited protective or causal effects on hepatitis. Intravenous injection of larger doses of LPS into normal mice, or intravenous antigen-challenge to sensitized mice, induced pulmonary platelet accumulation (PPA), as well as HPA. These reactions occurred "within a few min" of the LPS injection or antigen challenge and resulted in shock. Intravenous injection of 5HT or a catecholamine induced a rapid PPA "within 6 s." Intravenous LPS injection, within a minute, increased the pulmonary catecholamines that mediate the LPS-induced PPA. Macrophage-depletion from liver and spleen induced "day-scale" splenic platelet accumulation, suggesting the spleen is involved in clearing senescent platelets. These findings indicate the usefulness of 5HT as a marker of platelet behaviors, and provide a basis for a discussion of the roles of platelets as both "defenders" and "guardians."

  37. Effect of tsunami drill experience on evacuation behavior after the onset of the Great East Japan Earthquake 査読有り

    Nakaya Naoki, Nemoto Harumi, Yi Carine, Sato Ayako, Shingu Kotomi, Shoji Tomoka, Sato Shosuke, Tsuchiya Naho, Nakamura Tomohiro, Narita Akira, Kogure Mana, Sugawara Yumi, Yu Zhiqian, Gunawansa Nicole, Kuriyama Shinichi, Murao Osamu, Sato Takeshi, Imamura Fumihiko, Tsuji Ichiro, Hozawa Atsushi, Tomita Hiroaki

    INTERNATIONAL JOURNAL OF DISASTER RISK REDUCTION　28　206-213　2018年6月

    DOI： 10.1016/j.ijdrr.2018.02.037 　

    ISSN：2212-4209

  38. Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain 査読有り

    Mai Sakai, Hikaru Takeuchi, Zhiqian Yu, Yoshie Kikuchi, Chiaki Ono, Yuta Takahashi, Fumiaki Ito, Hiroo Matsuoka, Osamu Tanabe, Jun Yasuda, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Tomita

    Psychiatry and Clinical Neurosciences　72　(6)　409-422　2018年6月1日

    出版者・発行元： Blackwell Publishing

    DOI： 10.1111/pcn.12649 　

    ISSN：1440-1819 1323-1316

    eISSN：1440-1819

  39. The VEGF gene polymorphism impacts brain volume and arterial blood volume. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Atsushi Sekiguchi, Rui Nouchi, Yuka Kotozaki, Seishu Nakagawa, Carlos Makoto Miyauchi, Kunio Iizuka, Ryoichi Yokoyama, Takamitsu Shinada, Yuki Yamamoto, Sugiko Hanawa, Tsuyoshi Araki, Keiko Kunitoki, Yuko Sassa, Ryuta Kawashima

    Human brain mapping　38　(7)　3516-3526　2017年7月

    DOI： 10.1002/hbm.23606 　

    ISSN：1065-9471

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    Vascular endothelial growth factor (VEGF) plays a critical role in the angiogenesis and proliferation of various types of cells such as neurons, astroglia, and endothelial cells in the brain. A common polymorphism in the VEGF gene (-2578 C/A) is associated with circulating VEGF levels, cancers and Alzheimer's disease. Nonetheless, the effects of this polymorphism on normal human brain volume, arterial blood volume, and blood supply remain unclear. In this study, the effects of this polymorphism on the total gray matter volume (TGMV) and total white matter volume (TWMV) using T1-weighted structural images and the total arterial blood volume (TABV) and mean cerebral blood flow (mCBF) during rest using arterial spin labeling (ASL) in 765 young adult humans were investigated. Voxel-by-voxel whole-brain analyses of these measures were also performed. Multiple regression analyses with age and sex as covariates revealed that the VEGF genotype (number of C alleles) was significantly and positively correlated with TGMV, TWMV, and TABV as well as with regional gray and white matter volumes in widespread areas and regional arterial blood volume in some areas with high arterial blood volume. However, these regional associations were not seen when the corresponding global signal was included as a covariate in the multiple regression analyses, indicating that we failed to obtain evidence of region-specific associations between these brain measures and the genotype. The results suggest that the VEGF-2578C allele, is associated with changes in the vascular system that lead to increased blood volume and larger brain volume. Hum Brain Mapp 38:3516-3526, 2017. © 2017 Wiley Periodicals, Inc.

  40. グリア線維酸性蛋白質遺伝子多型の脳構造への影響の検討 精神疾患感受性メカニズムの理解に向けて

    高橋 雄太, 伊藤 文晃, 竹内 光, 坂井 舞, 兪 志前, 松岡 洋夫, 瀧 靖之, 川島 隆太, 富田 博秋

    精神神経学雑誌　(2017特別号)　S622-S622　2017年6月

    出版者・発行元： (公社)日本精神神経学会

    ISSN：0033-2658

  41. Pulmonary platelet accumulation induced by catecholamines: Its involvement in lipopolysaccharide-induced anaphylaxis-like shock 査読有り

    Zhiqian Yu, Hiroko Saito, Hirotada Otsuka, Yosuke Shikama, Hiromi Funayama, Mai Sakai, Shigeo Murai, Masanori Nakamura, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　43　40-52　2017年2月

    DOI： 10.1016/j.intimp.2016.11.034 　

    ISSN：1567-5769

    eISSN：1878-1705

  42. Microglial production of TNF-alpha is a key element of sustained fear memory 査読有り

    Zhiqian Yu, Tiotaka Fukushima, Chiaki Ono, Mai Sakai, Yoshiyuki Kasahara, Yoshie Kikuchi, Nicole Gunawansa, Yuta Takahashi, Hiroo Matsuoka, Satoshi Kida, Hiroaki Tomita

    BRAIN BEHAVIOR AND IMMUNITY　59　313-321　2017年1月

    DOI： 10.1016/j.bbi.2016.08.011 　

    ISSN：0889-1591

    eISSN：1090-2139

  43. リチウム投与下でのミクログリアと単球の遺伝子発現プロフィールの検討

    高橋 雄太, 兪 志前, 坂井 舞, 小松 浩, 伊藤 文晃, 松岡 洋夫, 富田 博秋

    精神神経学雑誌　(2016特別号)　S481-S481　2016年6月

    出版者・発行元： (公社)日本精神神経学会

    ISSN：0033-2658

  44. Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatric Disorders 査読有り

    Yuta Takahashi, Zhiqian Yu, Mai Sakai, Hiroaki Tomita

    FRONTIERS IN CELLULAR NEUROSCIENCE　10　144　2016年6月

    DOI： 10.3389/fncel.2016.00144 　

    ISSN：1662-5102

  45. Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders 査読有り

    Mai Sakai, Yuta Takahashi, Zhiqian Yu, Hiroaki Tomita

    Advances in Neuroimmune Biology　6　(2)　83-93　2016年

    出版者・発行元： IOS Press

    DOI： 10.3233/NIB-160110 　

    ISSN：1878-9498 1878-948X

    eISSN：1878-9498

  46. Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Atsushi Sekiguchi, Rui Nouchi, Yuka Kotozaki, Seishu Nakagawa, Carlos Makoto Miyauchi, Kunio Iizuka, Ryoichi Yokoyama, Takamitsu Shinada, Yuki Yamamoto, Sugiko Hanawa, Tsuyoshi Araki, Hiroshi Hashizume, Keiko Kunitoki, Yuko Sassa, Ryuta Kawashima

    NeuroImage　110　124-35　2015年4月15日

    DOI： 10.1016/j.neuroimage.2015.01.053 　

    ISSN：1053-8119

    詳細を見る 詳細を閉じる

    The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases.

  47. Therapeutic Concentration of Lithium Stimulates Complement C3 Production in Dendritic Cells and Microglia via GSK-3 Inhibition 査読有り

    Zhiqian Yu, Chiaki Ono, Setsuya Aiba, Yoshie Kikuchi, Ichiro Sora, Hiroo Matsuoka, Hiroaki Tomita

    GLIA　63　(2)　257-270　2015年2月

    DOI： 10.1002/glia.22749 　

    ISSN：0894-1491

    eISSN：1098-1136

  48. The associations among the dopamine D2 receptor Taq1, emotional intelligence, creative potential measured by divergent thinking, and motivational state and these associations' sex differences. 国際誌 査読有り

    Hikaru Takeuchi, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Atsushi Sekiguchi, Rui Nouchi, Yuka Kotozaki, Seishu Nakagawa, Carlos M Miyauchi, Kunio Iizuka, Ryoichi Yokoyama, Takamitsu Shinada, Yuki Yamamoto, Sugiko Hanawa, Tsuyoshi Araki, Hiroshi Hashizume, Keiko Kunitoki, Yuko Sassa, Ryuta Kawashima

    Frontiers in psychology　6　912-912　2015年

    DOI： 10.3389/fpsyg.2015.00912 　

    詳細を見る 詳細を閉じる

    Previous neuroscientific studies have shown that the dopaminergic system plays an important role in creative potential measured by divergent thinking (CPMDT), emotional control, and motivational state. However, although associations between two of these four components have been previously established (e.g., the association between CPMDT and emotional control, the association between CPMDT and motivational state, etc.), the interactions between these four remain unknown. The purpose of this study was to reveal these interactions using path analyses. The Taq1A polymorphism of the dopamine D2 receptor (DRD2) gene was used for this purpose. For measuring emotional intelligence (EI), we used the Japanese version of the Emotional Intelligence Scale. CPMDT was measured using the S-A creativity test. Motivational state was measured using the Vigor subscale of the Japanese version of the Profile of Mood Scale (POMS). Data from 766 healthy, right-handed individuals (426 men and 340 women; 20.7 ± 1.9 years of age) were used in this study. There were significant and robust positive relationships among measures of CPMDT, EI, and motivational state across sex. In addition, the polymorphism of the DRD2 gene was significantly associated with EI, specifically in females. Path analysis in females indicates that the model in which (a) the DRD2 polymorphism primarily facilitates EI, (b) EI in turn facilitates CPMDT and leads to a better motivational state, and (c) a better motivational state also directly facilitates CPMDT explains the data in the most accurate manner. This study suggested a comprehensive picture of the cascade of the associations among dopamine, EI, motivational state, and CPMDT at least in females.

  49. Fluorescently Activated Cell Sorting Followed by Microarray Profiling of Helper T Cell Subtypes from Human Peripheral Blood 査読有り

    Chiaki Ono, Zhiqian Yu, Yoshiyuki Kasahara, Yoshie Kikuchi, Naoto Ishii, Hiroaki Tomita

    PLOS ONE　9　(11)　e111405　2014年11月

    DOI： 10.1371/journal.pone.0111405 　

    ISSN：1932-6203

  50. Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury 査読有り

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

    AMERICAN JOURNAL OF PATHOLOGY　184　(9)　2505-2515　2014年9月

    DOI： 10.1016/j.ajpath.2014.05.015 　

    ISSN：0002-9440

    eISSN：1525-2191

  51. Prime role of bone IL-1 in mice may lie in emergency Ca2+-supply to soft tissues, not in bone-remodeling 査読有り

    Xue Deng, Senri Oguri, Hiromi Funayama, Yuko Ohtaki, Masafumi Ohsako, Zhiqian Yu, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　14　(4)　658-664　2012年12月

    DOI： 10.1016/j.intimp.2012.10.001 　

    ISSN：1567-5769

  52. Roles of platelets and macrophages in the protective effects of lipopolysaccharide against concanavalin A-induced murine hepatitis. 査読有り

    Zhiqian Yu, Hirotada Otsuka, Kouji Yamaguchi, Toshinobu Kuroishi, Takashi Sasano, Shunji Sugawara, Masanori Nakamura, Yasuo Endo

    Biochimica et biophysica acta　1812　(9)　1069-1079　2011年9月

    DOI： 10.1016/j.bbadis.2011.06.005 　

    ISSN：0925-4439

  53. Four mood stabilizers commonly induce FEZ1 expression in human astrocytes 査読有り

    Zhiqian Yu, Chiaki Ono, Helen B. Kim, Hiroshi Komatsu, Yoichiro Tanabe, Nobutaka Sakae, Keiichi I. Nakayama, Hiroo Matsuoka, Ichiro Sora, William E. Bunney, Hiroaki Tomita

    BIPOLAR DISORDERS　13　(5-6)　486-499　2011年8月

    DOI： 10.1111/j.1399-5618.2011.00946.x 　

    ISSN：1398-5647

  54. Effect of chronic lithium treatment on gene expression profile in mouse microglia and brain dendritic cells 査読有り

    Zhiqian Yu, Chiaki Ono, Ichiro Sora, Hiroaki Tomita

    Japanese Journal of Neuropsychopharmacology　31　(2)　101-102　2011年4月

    ISSN：1340-2544

  55. Effect of chronic lithium treatment on gene expression profile in mouse microglia and brain dendritic cells 査読有り

    Zhiqian Yu, Chiaki Ono, Yoichiro Tanabe, Ichiro Sora, Hiroaki Tomita

    NEUROSCIENCE RESEARCH　71　E122-E122　2011年

    DOI： 10.1016/j.neures.2011.07.522 　

    ISSN：0168-0102

  56. 気分安定薬バルプロ酸およびラモトリギン投与によるヒト脳細胞遺伝子発現変化のマイクロアレイ解析による包括的検討

    田邊 陽一郎, 田中 千晶, 兪 志前, 小松 浩, 木村 好, 羽藤 愛, 松岡 洋夫, 曽良 一郎, 富田 博秋

    Bipolar Disorder　8　61-69　2010年6月

    出版者・発行元： アルタ出版(株)

  57. Rejection of intradermally injected syngeneic tumor cells from mice by specific elimination of tumor-associated macrophages with liposome-encapsulated dichloromethylene diphosphonate, followed by induction of CD11b(+)/CCR3(-)/Gr-1(-) cells cytotoxic against the tumor cells 査読有り

    Takeshi Takahashi, Minenori Ibata, Zhiqian Yu, Yosuke Shikama, Yasuo Endo, Yasunori Miyauchi, Masanori Nakamura, Junko Tashiro-Yamaji, Sayako Miura-Takeda, Tetsunosuke Shimizu, Masashi Okada, Koichi Ueda, Takahiro Kubota, Ryotaro Yoshida

    CANCER IMMUNOLOGY IMMUNOTHERAPY　58　(12)　2011-2023　2009年12月

    DOI： 10.1007/s00262-009-0708-5 　

    ISSN：0340-7004

  58. Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice 査読有り

    Zhiqian Yu, Mami Ohba, Masanori Nakamura, Takashi Sasano, Masao Ono, Shunji Sugawara, Yasuo Endo

    THROMBOSIS AND HAEMOSTASIS　102　(6)　1251-1258　2009年12月

    DOI： 10.1160/TH08-06-0406 　

    ISSN：0340-6245

  59. Hepatic platelet accumulation in Fas-mediated hepatitis in mice 査読有り

    Yuko Ohtaki, Kouji Yamaguchi, Zhiqian Yu, Hiroyuki Kumamoto, Hidetoshi Shimauchi, Yoichiro Iwakura, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　9　(9)　1071-1078　2009年8月

    DOI： 10.1016/j.intimp.2009.04.016 　

    ISSN：1567-5769

  60. Induction of serum IL-18 with Propionibacterium acnes and lipopolysaccharide in phagocytic macrophage-inactivated mice 査読有り

    Takashi Nishioka, Toshinobu Kuroishi, Yumiko Sugawara, Zhiqian Yu, Takashi Sasano, Yasuo Endo, Shunji Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　82　(2)　327-334　2007年8月

    DOI： 10.1189/jlb.1006598 　

    ISSN：0741-5400

    eISSN：1938-3673

  61. Histidine decarboxylase-stimulating and inflammatory effects of alendronate in mice: Involvement of mevalonate pathway, TNF alpha, macrophages, and T-cells 査読有り

    Xue Deng, Zhiqian Yu, Hiromi Funayama, Kouji Yamaguchi, Takashi Sasano, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　7　(2)　152-161　2007年2月

    DOI： 10.1016/j.intimp.2006.09.009 　

    ISSN：1567-5769

  62. Inductions of histidine decarboxylase in mouse tissues following systemic antigen challenge: Contributions made by mast cells, non-mast cells and IL-1 査読有り

    Xue Deng, Xia Wu, Zhiqian Yu, Iwao Arai, Takashi Sasano, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY　144　(1)　69-78　2007年

    DOI： 10.1159/000102617 　

    ISSN：1018-2438

  63. Lipopolysaccharide stimulates histamine-forming enzyme (histidine decarboxylase) activity in murine dental pulp and gingiva 査読有り

    Noriaki Shoji, Atsushi Yoshida, Zhiqian Yu, Yasuo Endo, Takashi Sasano

    ARCHIVES OF ORAL BIOLOGY　51　(10)　856-860　2006年10月

    DOI： 10.1016/j.archoralbio.2006.04.004 　

    ISSN：0003-9969

  64. Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate 査読有り

    Xue Deng, Zhiqian Yu, Hiromi Funayama, Noriaki Shoji, Takashi Sasano, Yoichiro Iwakura, Shunji Sugawara, Yasuo Endo

    TOXICOLOGY AND APPLIED PHARMACOLOGY　213　(1)　64-73　2006年5月

    DOI： 10.1016/j.taap.2005.09.005 　

    ISSN：0041-008X

  65. Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice. 国際誌 査読有り

    Kouji Yamaguchi, Zhiqian Yu, Hiroyuki Kumamoto, Yumiko Sugawara, Hiroshi Kawamura, Haruhiko Takada, Takashi Yokochi, Shunji Sugawara, Yasuo Endo

    Biochimica et biophysica acta　1762　(3)　269-275　2006年3月

    DOI： 10.1016/j.bbadis.2005.11.010 　

    ISSN：0006-3002

  66. Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice 国際誌 査読有り

    K Ikawa, T Nishioka, ZQ Yu, Y Sugawara, J Kawagoe, T Takizawa, Primo, V, B Nikolic, T Kuroishi, T Sasano, H Shimauchi, H Takada, Y Endo, S Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　78　(5)　1118-1126　2005年11月

    DOI： 10.1189/jlb.0305151 　

    ISSN：0741-5400

  67. Comparative appraisal of clodronate, aspirin and dexamethasone as agents reducing alendronate-induced inflammation in a murine model 査読有り

    Zhiqian Yu, Hiromi Funayama, Xue Deng, Toshinobu Kuroishi, Takashi Sasano, Shunji Sugawara, Yasuo Endo

    BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY　97　(4)　222-229　2005年10月

    DOI： 10.1111/j.1742-7843.2005.pto_138.x 　

    ISSN：1742-7835

  68. Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome 査読有り

    Zhiqian Yu, Yuko Ohtaki, Kenzou Kai, Takashi Sasano, Hidetoshi Shimauchi, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Katsuo Kumagai, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　5　(3)　571-580　2005年3月

    DOI： 10.1016/j.intimp.2004.11.004 　

    ISSN：1567-5769

  69. Scratching behavior in NC/Nga mice with dermatitis: Involvement of histamine-induced itching 査読有り

    Yuki Hashimoto, Norikazu Takano, Atsushi Nakamura, Shiro Nakaike, Zhiqian Yu, Yasuo Endo, Iwao Arai

    Allergology International　53　(4)　349-358　2004年

    出版者・発行元： Blackwell Publishing

    DOI： 10.1111/j.1440-1592.2004.00358.x 　

    ISSN：1323-8930

︎全件表示 ︎最初の5件までを表示

MISC 37

  1. ヒト死後脳組織の網羅的遺伝子発現解析に対する交絡因子の影響についての検討

    旗野将貴, 宮原一総, 日野瑞城, 日野瑞城, 長岡敦子, 長岡敦子, 兪志前, 林秀樹, 柿田明美, 富田博秋, 三浦至, 國井泰人, 國井泰人

    日本生物学的精神医学会(Web)　45th　2023年

  2. 産後うつ病の予測と予防のための血漿サイトカインレベルの検証

    兪 志前, 小野 千晶, 小原 拓, 菊地 沙耶, 小林 奈津子, 菅原 準一, 栗山 進一, 山本 雅之, 八重樫 伸生, 富田 博秋

    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　195-195　2020年8月

    出版者・発行元： 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

  3. オリゴデンドロサイト関連遺伝子多型(rs1059004)と自己スキーマ及び抑うつ症状との相関研究

    小松浩, 小松浩, 竹内光, 菊地淑恵, 小野千晶, 兪志前, 兪志前, 飯塚邦夫, 角藤芳久, 舩越俊一, 舩越俊一, 大野高志, 川島隆太, 川島隆太, 川島隆太, 瀧靖之, 瀧靖之, 瀧靖之, 富田博秋, 富田博秋, 富田博秋, 富田博秋

    日本うつ病学会総会プログラム・抄録集　16th　2019年

  4. Pregnant mice exposure to extreme level of oxytocin influences emotional and social behaviors of the offsprings after growing up

    Yoshiyuki Kasahara, Sachie Suzuki, Yuji Onouchi, Ayaka Yoshida, Chiaki Ono, Yoshie Kikuchi, Zhiqian Yu, Hiroaki Tomita

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY　19　50-50　2016年6月

    ISSN： 1461-1457

    eISSN： 1469-5111

  5. Association between mu-opioid receptor gene variant 118 A &gt; G and personality traits among Japanese population

    Yumiko Kubo, Hikaru Takeuchi, Yoshie Kikuchi, Yoshiyuki Kasahara, Zhiqian Yu, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Tomita

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY　19　299-300　2016年6月

    ISSN： 1461-1457

    eISSN： 1469-5111

  6. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 希少遺伝性難病の精神発達に関する病態解明のための網羅的分子遺伝学的研究

    富田博秋, 福與なおみ, 小野千晶, 兪志前

    次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 平成25年度 総括・分担研究報告書　61-63　2014年

  7. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 希少遺伝性難病の精神発達に関する病態解明のための網羅的分子遺伝学的研究

    富田博秋, 福與なおみ, 小野千晶, 兪志前

    次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 平成23-25年度 総合研究報告書　69-73　2014年

  8. FACS-arrayによる統合失調症罹患者のTh1およびTh2細胞の遺伝子発現プロファイリング

    小野千晶, 兪志前, 小松浩, 小松浩, 石井直人, 曽良一郎, 富田博秋

    統合失調症研究　2　(1)　2012年

  9. 双極性障害治療薬のアストロサイトにおける発現プロファイルの影響.

    兪 志前, 小野 千晶, 田邊 陽一郎, 小松 浩, 松岡 洋夫, 曽良 一郎, 富田 博秋, 双極性障害治療薬のアストロサイトにおける発現プロファイルの影響

    Bipolar Disorder　(9)　13-14　2011年9月

  10. 双極性障害治療薬のアストロサイトにおける発現プロファイルへの影響

    兪 志前, 小野 千晶, 田邊 陽一郎, 小松 浩, 松岡 洋夫, 曽良 一郎, 富田 博秋

    Bipolar Disorder　9　13-14　2011年5月

    出版者・発行元： アルタ出版(株)

  11. 統合失調症罹患者のTh1およびTh2細胞のマイクロアレイ遺伝子発現プロファイリング

    小野千晶, 兪志前, 田邊陽一郎, 田邊陽一郎, 小松浩, 小松浩, 曽良一郎, 松岡洋夫, 石井直人, 富田博秋

    統合失調症研究　1　(1)　2011年

  12. FACS-microarray study of immune cells from patients with schizophrenia

    Chiaki Ono, Zhiqian Yu, Yoichiro Tanabe, Naoto Ishii, Hiroaki Tomita

    NEUROSCIENCE RESEARCH　71　E366-E366　2011年

    DOI： 10.1016/j.neures.2011.07.1604 　

    ISSN： 0168-0102

  13. 統合失調症の陰性症状の進行に関わる精神神経免疫学的メカニズムに関する研究．

    富田博秋, 小野千晶, 兪志前

    こころの健康と病気　119-131　2011年

  14. ソトス症候群罹患者リンパ芽球のマイクロアレイ解析~NSD1の下流で発現調節を受ける遺伝子群の検索~

    富田博秋, 小野千晶, 兪志前, 田邊陽一郎, 福與なおみ, 西村章, 黒滝直弘, 黒澤健司, 岡本伸彦, 松本直通

    日本人類遺伝学会大会プログラム・抄録集　55th　174　2010年10月8日

  15. 気分安定薬のアストロサイトにおける軸索誘導タンパク発現の誘導

    兪志前, 小野千晶, 田邊陽一郎, 田邊陽一郎, 小松浩, 小松浩, 松岡洋夫, 曽良一郎, 富田博秋

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　20th-40th　124-124　2010年

    出版者・発行元： 日本臨床精神神経薬理学会・日本神経精神薬理学会

  16. Comprehensive gene expression analysis of SK-N-SH cells after Lamotrigine treatment

    Yoichiro Tanabe, Zhiqian Yu, Chiaki Ono, Ai Hato, Hiroo Matsuoka, Hiroaki Tomita

    NEUROSCIENCE RESEARCH　68　E317-E317　2010年

    DOI： 10.1016/j.neures.2010.07.1409 　

    ISSN： 0168-0102

  17. Effect of chronic lithium treatment on gene expression profile in mouse microglia and brain dendritic cells

    Z. Yu, C. Ono, Y. Tanabe, I. Sora, H. Tomita

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY　13　133-134　2010年

    ISSN： 1461-1457

  18. Mood stabilizers-mediated gene expression in human astrocytes

    Zhiqian Yu, Chiaki Ono, Yoichiro Tanabe, Ichiro Sora, Hiroaki Tomita

    NEUROSCIENCE RESEARCH　68　E317-E317　2010年

    DOI： 10.1016/j.neures.2010.07.1407 　

    ISSN： 0168-0102

  19. 気分安定薬のアストロサイトにおける軸索誘導タンパク発現の誘導 (日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集)

    兪 志前, 小野 千晶, 田邊 陽一郎, 小松 浩, 松岡 洋夫, 曽良 一郎, 富田 博秋

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　20回・40回　124-124　2010年

  20. 統合失調症罹患者のTh1およびTh2細胞のマイクロアレイ遺伝子発現プロファイリング (日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集)

    小野 千晶, 兪 志前, 田邊 陽一郎, 小松 浩, 松岡 洋夫, 曽良 一郎, 石井 直人, 富田 博秋

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　20回・40回　151-151　2010年

  21. 双極性障害治療薬のアストロサイトにおける遺伝子発現変化の包括的検討 (神経化学)

    兪 志前, 小野 千晶, 田邊 陽一郎, 曽良 一郎, 富田 博秋

    神経化学　49　(2月3日)　676-676　2010年

  22. 気分安定薬奏功機序解明のための包括的遺伝子発現解析

    富田 博秋, 田中 千晶, 兪 志前, 小松 浩, 木村 好, 曽良 一郎, ヘレン・B.・キム, ウィリアム・E.・バニー

    臨床薬理の進歩　(30)　52-59　2009年7月

    出版者・発行元： (公財)臨床薬理研究振興財団

    ISSN： 0914-4366

  23. 【精神疾患のブレインバンク設立に向けて】交絡因子に配慮した脳バンク構築の必要性

    富田 博秋, 田中 千晶, 兪 志前

    脳と精神の医学　20　(1)　17-24　2009年3月

    出版者・発行元： 日本生物学的精神医学会

    DOI： 10.11249/jsbp.20.17 　

    ISSN： 0915-7328

    eISSN： 1884-779X

  24. 気分安定薬のアストロサイトにおける遺伝子発現変化の包括的検討

    兪志前, 田中千晶, 小松浩, 高橋怜史, 木村好, 曽良一郎, 富田博秋

    日本生物学的精神医学会プログラム・講演抄録　31st　2009年

  25. 気分安定薬リチウムの樹状細胞における遺伝子発現変化の包括的検討

    兪志前, 小野千晶, 田邊陽一郎, 田邊陽一郎, 小松浩, 小松浩, 木村好, 羽藤愛, 松岡洋夫, 曽良一郎, 富田博秋

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　19th-39th　2009年

  26. 気分調整薬がヒト神経由来細胞およびグリア由来細胞の各BDNF転写物バリアント発現量に及ぼす影響の検討

    小松浩, 田中千晶, 兪志前, 木村好, 高橋さとし, 曽良一郎, 松岡洋夫, 富田博秋

    日本生物学的精神医学会プログラム・講演抄録　30th　2008年

  27. Concanavalin A肝炎のLPS前投与による抑制:血小板とマクロファージの関与

    兪 志前, 山口 晃史, Deng Xue, 黒石 智誠, 一石 英一郎, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　37　190-190　2007年10月

    出版者・発行元： (NPO)日本免疫学会

    ISSN： 0919-1984

  28. Propionibacterium acnes/LPS処理したマウスのケラチノサイト上皮細胞からの血清IL-18産生誘導．

    西岡貴志, 兪志前, 菅原由美子, 笹野高嗣, 遠藤康男, 菅原俊二

    歯科基礎医学会雑誌　48　(Supplement)　146　2006年9月

    ISSN： 1349-0079

  29. LPS 誘導性致死に対する血小板の役割（グリチルリチンの効果）．

    兪 志前

    東北大歯学誌　25　(1)　42-42　2006年

    ISSN： 0287-3915

  30. マウスにおける粘膜細胞からのIL-18誘導における好中球とprotease-activated receptor 2(PAR2)の関与

    西岡貴志, 伊川 桂次, 兪 志前, 菅原 由美子, 遠藤 康男, 菅原 俊二

    日本免疫学会総会・学術集会記録　35　183-183　2005年11月

    出版者・発行元： (NPO)日本免疫学会

    ISSN： 0919-1984

  31. Lipopolysaccharide stimulates histamine-forming enzyme (histidine decarboxylase) activity in murine dental pulp and gingiva

    N. Shoji, A. Yoshida, Z. Yu, Y. Endo, T. Sasano

    International Congress Series　1284　207-208　2005年9月

    DOI： 10.1016/j.ics.2005.07.032 　

    ISSN： 0531-5131

  32. in vivoでの粘膜細胞からのIL-18誘導における好中球とprotease-activated receptor-2(PAR-2)の関与

    西岡貴志, 伊川 桂次, 兪 志前, 菅原 由美子, 笹野 高嗣, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　99-99　2005年9月

    出版者・発行元： (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  33. Adrenalineに対するin vivoにおける血小板の反応.

    兪 志前, 菅原 俊二, 遠藤 康男

    歯科基礎医学会雑誌　46　(5)　473-473　2004年9月

    出版者・発行元： 歯科基礎医学会

    ISSN： 1349-0079

  34. Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells

    YU Z.

    Cancer Lett　215　159-166　2004年

  35. 3.LPSに対する血小板反応のグリチルリチンによる抑制(一般演題)(第42国東北大学歯学会講演抄録)

    兪 志前, 笹野 高嗣, 遠藤 康男, 東北大学大学院歯学研究科口腔診断・放射線学分野:東北大学歯科薬理学分野, 東北大学大学院歯学研究科口腔診断・放射線学分野, 東北大学歯科薬理学分野

    東北大学歯学雑誌 = Tohoku University dental journal　22　(1)　54-54　2003年6月30日

    ISSN： 0287-3915

  36. Alendronateの炎症作用：Dexamethasoneの効果.

    兪 志前

    歯科基礎医学会雑誌　45　(5)　372　2003年

  37. Depressed [Ca^<2+>]_i responses to isoproterenol and cAMP in isolated cardiomyocytes from experimental diabetic rats

    YU Z

    Am J Physiol Heart Circ Physiol　266　H2334-H2342　1994年

︎全件表示 ︎最初の5件までを表示

産業財産権 3

  1. Toxin Removal Amount Measuring Method and Sampling Device

    兪 志前

    産業財産権の種類: 特許権

  2. Method for Gene Analysis and System

    兪 志前

    産業財産権の種類: 特許権

  3. Solutions for RNA Stabilization and Storage

    兪 志前

    産業財産権の種類: 特許権

共同研究・競争的資金等の研究課題 3

  1. オートファジーを介したうつ病の分子機構解明と新規治療法の開発

    兪 志前

    2020年4月1日 ～ 2023年3月31日

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    ストレスはうつ様行動を引き起こし、オートファジーはストレス条件下で活性化されることが考えられる。本研究では反復社会挫折ストレス (Repeated social defeat; RSD) による行動変化、およびミクログリアにおけるオートファジーの関与を明らかにすることを目的とした。RSD を負荷したマウスは、脳内における初期のオートファジーシグナル (initial autophagy signaling) の活性が観察された。その中、前頭前野でのオートファジー関連遺伝子（Atg6、Atg7、およびAtg12） の発現増加を見出したが、海馬においてはオートファジーの変動が見られなかった。同様に、うつ病患者の死後脳の前頭前野においても、ATG （Atg6、Atg7、Atg12、およびAtg5） の有意な遺伝子の発現増加が明らかになった。また、マウスの前頭前野におけるオートファゴソーム結合タンパク質 LC3B が有意に増加した一方、オートファゴソーム分解マーカーである p62 は耐性群マウスで有意に減少した。しかし、脆弱性群マウスや うつ病患者において、LC3B および p62 の変動は見られなかった。以上の結果から、オートファジーフラックス (autophagic flux) の亢進がストレス誘発したうつ様行動を軽減する可能性が示唆された。さらに、initial autophagy signaling の制御因子である FKBP5 が耐性群マウスの前頭前野で遺伝子転写およびタンパク質レベルで有意に増加した。また、耐性群マウスにおいて、前頭前野のミクログリアにおける autophagic flux の亢進を示し、ミクログリアのオートファジー欠損 (Cx3cr1Cre+;Atg7flox/flox) によって、RSD 誘発した回避行動を悪化させた。

  2. 統合失調症における環境要因のエピゲノム解析と分子病態の解明

    兪 志前, 富田 博秋, 長﨑 正朗, 中山 啓子, 橋本 謙一, 岩本 和也, 木下 賢吾

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (C)

    研究機関：Tohoku University

    2016年4月1日 ～ 2019年3月31日

    詳細を見る 詳細を閉じる

    胎生期の母体感染が胎児の脳発達に影響を及ぼし、成長後の統合失調症の発症率を高めることが知られている。母体感染による統合失調症の発症機構を解明するために、統合失調症モデルマウスを用い、脳内の遺伝子発現およびDNAメチル化の変化を全ゲノム規模で検討した。その結果、統合失調症の発症に関わる遺伝子を特定し、雌マウスにおいて顕著な発現変動が見られた。また、統合失調症の女性罹患者の死後脳においても、雌マウスと同様の変化が確認された。

  3. 精神神経免疫相関が関与する精神疾患病態のマイクロエンドフェノタイプの解明

    富田 博秋, 兪 志前

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

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

    研究機関：Tohoku University

    2012年6月28日 ～ 2017年3月31日

    詳細を見る 詳細を閉じる

    A03喜田との共同研究から、心的外傷後ストレス障害モデルマウスにおいて、ミクログリアのサイトカイン産生プロファイルが恐怖記憶の形成・維持のマイクロエンドフェノタイプとして有益であることを特定し、治療薬開発のストラテジーを確立した。また、A02橋本との胎生期の母体免疫ストレス負荷による統合失調症モデルマウスを用いた共同研究から、胎生期の母体免疫負荷に伴うグリア細胞関連遺伝子領域のメチル化状態変化を同疾患のマイクロエンドフェノタイプの候補として特定した。更に、精神疾患に関与する免疫細胞サブポピュレーションの特定の技術開発、気分安定薬の薬効に関連する免疫関連マイクロエンドフェノタイプの特定を行った。