2025/07/10 更新

写真a

オウギダニ マサヒロ
扇谷 昌宏
OHGIDANI Masahiro
所属
医学部 医学科 基礎医学講座 解剖学講座(機能形態学分野)
外部リンク

研究キーワード

  • 解剖学

  • 精神神経疾患

  • トランスレーショナル研究

  • 医用生体工学

  • 神経免疫

  • 生物学的精神医学

  • ミクログリア

研究分野

  • ライフサイエンス / 解剖学

  • ライフサイエンス / 精神神経科学

論文

  • Expression of Kallikrein in Glial Cells and Its Influence on Oligodendrocyte Myelination. 査読 国際誌

    Yusuke Tanaka, Eriko Furube, Shigetaka Yoshida, Masahiro Ohgidani

    Journal of neurochemistry   169 ( 7 )   e70150   2025年7月

     詳細を見る

    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Appropriate myelin structures are crucial for efficient nerve impulse conduction; however, the precise mechanisms sustaining myelin integrity throughout life remain unclear. KLK6 and KLK8 (Klk8 in mice), serine proteases of the tissue kallikrein family, are upregulated in oligodendrocytes in response to central nervous system injuries and are associated with myelin degradation. However, the physiological roles of these proteases have not yet been fully clarified. Here, we examined whether Klk8 and Klk6 are expressed in glial cells other than oligodendrocytes and whether Klk8 affects myelin structure under physiological conditions. Microglia, oligodendrocytes, and astrocytes were isolated from the brains and spinal cords of wild-type and Klk8 knockout mice, and we examined the expression levels of Klk8, Klk6, and myelin-related genes. We found that both Klk6 and Klk8 expression levels in oligodendrocytes were correlated with myelin-related gene expression levels. The myelin-related gene expression levels in oligodendrocytes were significantly higher in Klk8 knockout mice than in wild-type mice. Immunohistochemistry, western blotting, and transmission electron microscopy revealed that, compared with that in wild-type mice, the myelin volume and thickness were greater in Klk8 knockout mice. Oligodendrocyte-expressed Klk8 may play a role in modulating myelin structure under physiological conditions. Klk8 expression was higher in microglia than in oligodendrocytes, and Klk6 expression was higher in astrocytes than in oligodendrocytes. The expression levels of Klk6 and Klk8 in microglia and astrocytes were uncorrelated with the expression of myelin-related genes in oligodendrocytes, suggesting that these genes in microglia and astrocytes may have functional roles other than myelination.

    DOI: 10.1111/jnc.70150

    PubMed

    researchmap

  • The flow cytometric analysis of depression focusing on modern-type depression and hikikomori: Exploring the link between subtypes of depression and immunological imbalances. 査読 国際誌

    Keitaro Matsuo, Mitsuru Watanabe, Shogo Inamine, Toshio Matsushima, Sota Kyuragi, Yasuhiro Maeda, Ryoko Katsuki, Masahiro Ohgidani, Ryo Yamasaki, Noriko Isobe, Tomohiro Nakao, Takahiro A Kato

    Dialogues in clinical neuroscience   27 ( 1 )   13 - 25   2025年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Depression includes different phenotypes. Modern-type depression (MTD) is a gateway disorder to pathological social withdrawal, known as hikikomori. Adverse childhood experiences (ACEs) are also important aetiologies of depression. Recently, immune imbalance has been proposed as a biological basis of depression. We hypothesised that peripheral immunological characteristics may be involved in subtyping of depression. METHODS: 21 patients with major depressive disorder (MDD) and 24 healthy controls (HC) were recruited. Peripheral blood mononuclear cells (PBMCs) were examined for surface antigens by flow cytometry. Participants were administered psychological scales such as Patient Health Questionnaire (PHQ)-9, Modern-Type Depression Trait Scale (TACS-22), Hikikomori Questionnaire (HQ-25), Child Abuse and Trauma Scale (CATS). RESULTS: MDD group showed significantly higher percentage of B cells than HC group (p = 0.032). MDD group presented a negative correlation between: PHQ-9 and CD8 T effector memory cells (r= -0.639, p = 0.002), TACS-22 and monocytes (r= -0.459, p = 0.036), HQ-25 and NK T cells (r= -0.638, p = 0.004), CATS and Intermediate monocytes (r= -0.594, p = 0.009). CONCLUSIONS: MTD traits, hikikomori tendencies, and ACEs were correlated with specific characteristics of peripheral immune cells. Our results suggest that immune imbalance influences the diverse presentations of depression. Further validation is warranted by large-scale prospective studies.

    DOI: 10.1080/19585969.2025.2452842

    PubMed

    researchmap

  • Human monocyte‐derived microglia‐like (<scp>iMG</scp>) cells: A tool to explore microglial dynamics 査読

    Sota Kyuragi, Shogo Inamine, Masahiro Ohgidani, Takahiro A. Kato

    Clinical and Experimental Neuroimmunology   2024年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Abstract

    Recent studies have highlighted the importance of microglia as key immunomodulators in a variety of neuropsychiatric diseases. Postmortem brain analysis and positron emission tomography are representative research approaches to assess microglial activation in human patients and this research has revealed microglial activation in the brains of patients with various neuropsychiatric disorders. However, only limited aspects of microglial activation can be assessed with these methods. To overcome the technical and ethical limitations of collecting human‐derived microglia in brain biopsies, we first developed a method to generate directly induced microglia‐like (iMG) cells from fresh human peripheral blood monocytes in 2014. These iMG cells can be used to perform dynamic morphological and molecular analyses regarding phagocytic capacity and cytokine release following stress stimulation at the cellular level. Patient‐derived iMG cells can potentially serve as an important surrogate marker for estimating microglial activation in the human brain, and may provide previously unknown insights into the dynamic pathophysiology of microglia in patients with neuropsychiatric disorders. Thus, the iMG‐based technology could be used as a valuable reverse translational tool and provide new insights into the dynamic molecular pathophysiology of microglia in a wide variety of psychiatric and physical disorders.

    DOI: 10.1111/cen3.12815

    researchmap

  • Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research. 査読 国際誌

    Sota Kyuragi, Shogo Inamine, Masahiro Ohgidani, Takahiro A Kato

    Journal of visualized experiments : JoVE   ( 211 )   2024年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recent investigations employing animal models have highlighted the significance of microglia as crucial immunological modulators in various neuropsychiatric and physical diseases. Postmortem brain analysis and positron emission tomography imaging are representative research methods that evaluate microglial activation in human patients; the findings have revealed the activation of microglia in the brains of patients presenting with various neuropsychiatric disorders and chronic pain. Nonetheless, the aforementioned technique merely facilitates the assessment of limited aspects of microglial activation. In lieu of brain biopsy and the induced pluripotent stem cell technique, we initially devised a technique to generate directly induced microglia-like (iMG) cells from freshly derived human peripheral blood monocytes by supplementing them with granulocyte-macrophage colony-stimulating factor and interleukin 34 for 2 weeks. These iMG cells can be employed to perform dynamic morphological and molecular-level analyses concerning phagocytic capacity and cytokine releases following cellular-level stress stimulation. Recently, comprehensive transcriptome analysis has been used to verify the similarity between human iMG cells and brain primary microglia. The patient-derived iMG cells may serve as key surrogate markers for predicting microglial activation in human brains and have aided in the unveiling of previously unknown dynamic pathophysiology of microglia in patients with Nasu-Hakola disease, fibromyalgia, bipolar disorder, and Moyamoya disease. Therefore, the iMG-based technique serves as a valuable reverse-translational tool and provides novel insights into elucidating dynamic the molecular pathophysiology of microglia in a variety of mental and physical diseases.

    DOI: 10.3791/66819

    PubMed

    researchmap

  • A high-fat diet influences neural stem and progenitor cell environment in the medulla of adult mice. 査読 国際誌

    Eriko Furube, Masahiro Ohgidani, Yusuke Tanaka, Seiji Miyata, Shigetaka Yoshida

    Neuroscience   559   64 - 76   2024年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It has been widely established that neural stem cells (NSCs) exist in the adult mammalian brain. The area postrema (AP) and the ependymal cell layer of the central canal (CC) in the medulla were recently identified as NSC niches. There are two types of NSCs: astrocyte-like cells in the AP and tanycyte-like cells in the CC. However, limited information is currently available on the characteristics and functional significance of these NSCs and their progeny in the AP and CC. The AP is a part of the dorsal vagal complex (DVC), together with the nucleus of the solitary tract (Sol) and the dorsal motor nucleus of the vagus (10 N). DVC is the primary site for the integration of visceral neuronal and hormonal cues that act to inhibit food intake. Therefore, we examined the effects of high-fat diet (HFD) on NSCs and progenitor cells in the AP and CC. Eight-week-old male mice were fed HFD for short (1 week) and long periods (4 weeks). To detect proliferating cells, mice consecutively received intraperitoneal injections of BrdU for 7 days. Brain sections were processed with immunohistochemistry using various cell markers and BrdU antibodies. Our data demonstrated that adult NSCs and neural progenitor cells (NPCs) in the medulla responded more strongly to short-term HFD than to long-term HFD. HFD increased astrocyte density in the Sol and 10 N, and increased microglial/macrophage density in the AP and Sol. Furthermore, long-term HFD induced mild inflammation in the medulla, suggesting that it affected the proliferation of NSCs and NPCs.

    DOI: 10.1016/j.neuroscience.2024.08.034

    PubMed

    researchmap

  • Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells. 査読 国際誌

    Kousuke Yonemoto, Fumihiko Fujii, Ryoji Taira, Masahiro Ohgidani, Katsuhide Eguchi, Sayaka Okuzono, Yuko Ichimiya, Yuri Sonoda, Pin Fee Chong, Hironori Goto, Hikaru Kanemasa, Yoshitomo Motomura, Masataka Ishimura, Yuhki Koga, Keita Tsujimura, Takao Hashiguchi, Hiroyuki Torisu, Ryutaro Kira, Takahiro A Kato, Yasunari Sakai, Shouichi Ohga

    Clinical immunology (Orlando, Fla.)   255   109756 - 109756   2023年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

    DOI: 10.1016/j.clim.2023.109756

    PubMed

    researchmap

  • Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease. 査読 国際誌

    Noritoshi Shirozu, Masahiro Ohgidani, Nobuhiro Hata, Shunya Tanaka, Shogo Inamine, Noriaki Sagata, Tetsuaki Kimura, Ituro Inoue, Koichi Arimura, Akira Nakamizo, Ataru Nishimura, Naoki Maehara, Soh Takagishi, Katsuma Iwaki, Tomohiro Nakao, Keiji Masuda, Yasunari Sakai, Masahiro Mizoguchi, Koji Yoshimoto, Takahiro A Kato

    Scientific reports   13 ( 1 )   14842 - 14842   2023年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

    DOI: 10.1038/s41598-023-41456-z

    PubMed

    researchmap

  • Ameliorative effects of Fingolimod (FTY720) on microglial activation and psychosis-related behavior in short term cuprizone exposed mice. 査読 国際誌

    Siyao Li, Koki Sakurai, Masahiro Ohgidani, Takahiro A Kato, Takatoshi Hikida

    Molecular brain   16 ( 1 )   59 - 59   2023年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Schizophrenia is a psychiatric disorder that affects around 1% of the population in widespread populations, with severe cases leading to long-term hospitalization and necessitation of lifelong treatment. Recent studies on schizophrenia have highlighted the involvement of inflammatory and immunoregulatory mechanisms with the onset of symptoms, and the usage of anti-inflammatory treatments are being tested against periods of rapid psychosis. In the central nervous system, microglia are the innate immune population which are activated in response to a wide range of physical and psychological stress factors and produce proinflammatory mediators such as cytokines. Microglial activation and neuroinflammation has been associated to numerous psychiatric disorders including schizophrenia, especially during psychotic episodes. Thus, novel treatments which dampen microglial activation may be of great relevance in the treatment of psychiatric disorders. Fingolimod (FTY720) is a drug used as an immunosuppressive treatment to multiple sclerosis. Recent clinical trials have focused on FTY720 as a treatment for the behavioral symptoms in schizophrenia. However, the mechanisms of Fingolimod in treating the symptoms of schizophrenia are not clear. In this study we use a recently developed neuroinflammatory psychosis model in mice: cuprizone short-term exposure, to investigate the effects of FTY720 administration. FTY720 administration was able to completely alleviate methamphetamine hypersensitivity caused by cuprizone exposure. Moreover, administration of FTY720 improved multiple measures of neuroinflammation (microglial activation, cytokine production, and leucocyte infiltration). In conclusion, our results highlight the future use of FTY720 as a direct anti-inflammatory treatment against microglial activation and psychosis.

    DOI: 10.1186/s13041-023-01047-5

    PubMed

    researchmap

  • Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter. 査読 国際誌

    Eriko Furube, Masahiro Ohgidani, Shigetaka Yoshida

    Neurochemical research   2023年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Axonal injury and demyelination occur in demyelinating diseases, such as multiple sclerosis, and the detachment of myelin from axons precedes its degradation. Paranodes are the areas at which each layer of the myelin sheath adheres tightly to axons. The destruction of nodal and paranodal structures during inflammation is an important pathophysiology of various neurological disorders. However, the underlying pathological changes in these structures remain unclear. Kallikrein 6 (KLK6), a serine protease produced by oligodendrocytes, is involved in demyelinating diseases. In the present study, we intraperitoneally injected mice with LPS for several days and examined changes in the localization of KLK6. Transient changes in the intracellular localization of KLK6 to paranodes in the spinal cord were observed during LPS-induced systemic inflammation. However, these changes were not detected in the upper part of brain white matter. LPS-induced changes were suppressed by minocycline, suggesting the involvement of microglia. Moreover, nodal lengths were elongated in LPS-treated wild-type mice, but not in LPS-treated KLK6-KO mice. These results demonstrate the potential involvement of KLK6 in the process of demyelination.

    DOI: 10.1007/s11064-023-03929-5

    PubMed

    researchmap

  • Neurotoxicity Assessment System for Metals Using Mixed Cultures of Neural and Glial Cell Lines 査読

    Ohgidani Masahiro, Furube Eriko, Tanaka Yusuke, Yoshida Shigetaka

    Alternatives to Animal Testing and Experimentation   28 ( 1 )   8 - 14   2023年

     詳細を見る

    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:Japanese Society for Alternative to Animal Experiments  

    Evaluations of the toxicity of hazardous substances in foods and other products are essential. Metals are severely neurotoxic to humans. To date, neurotoxicity has mainly been examined in animal experiments using rodents; however, the importance of using <i>in vitro</i> systems has recently been reported. Although the brain also contains glial cells, <i>in vitro</i> assessments of neurotoxicity have mainly been performed using neurons. Therefore, we established a high-throughput evaluation system by creating a mixed culture system of microglia, a type of glial cell, and neurons using BV2 and Neuro2A cells. The mixed culture showed changes in gene expression compared to the monoculture. Furthermore, in examinations of the toxicities of various metals, some exhibited different toxicities in the mixed culture from those in the single culture. These results suggest that the conventional evaluation system using single cultures is insufficient and also that the use of glial cells to accurately assess neurotoxicity may be necessary.

    DOI: 10.11232/aatex.28.8

    CiNii Research

    researchmap

  • A case of bipolar disorder with <i>AIF1</i> (coding gene of Iba‐1) deletion: A pilot <i>in vitro</i> analysis using blood‐derived microglia‐like cells 査読

    Masahiro Ohgidani, Itaru Kushima, Shogo Inamine, Sota Kyuragi, Noriaki Sagata, Tomohiro Nakao, Shigenobu Kanba, Norio Ozaki, Takahiro A Kato

    Psychiatry and Clinical Neurosciences   77 ( 2 )   128 - 130   2022年11月

     詳細を見る

    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/pcn.13505

    researchmap

    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pcn.13505

  • Preliminary analysis of hippocampus synaptic apoptosis and microglial phagocytosis induced by severe restraint stress 査読

    Shingo Enomoto, Masahiro Ohgidani, Noriaki Sagata, Shogo Inamine, Takahiro A. Kato

    Neuropsychopharmacology Reports   43 ( 1 )   120 - 125   2022年11月

     詳細を見る

    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/npr2.12298

    researchmap

    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/npr2.12298

  • Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro 査読

    Toru Murakawa-Hirachi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshinori Haraguchi, Akira Monji

    Scientific Reports   11 ( 1 )   2021年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-021-85625-4

    Scopus

    PubMed

    researchmap

  • Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study 査読

    Hiroaki Kubo, Daiki Setoyama, Motoki Watabe, Masahiro Ohgidani, Kohei Hayakawa, Nobuki Kuwano, Mina Sato-Kasai, Ryoko Katsuki, Shigenobu Kanba, Dongchon Kang, Takahiro A. Kato

    Scientific Reports   11 ( 1 )   2021年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-020-75115-4

    Scopus

    PubMed

    researchmap

  • CD206 Expression in Induced Microglia-Like Cells From Peripheral Blood as a Surrogate Biomarker for the Specific Immune Microenvironment of Neurosurgical Diseases Including Glioma 査読

    Shunya Tanaka, Masahiro Ohgidani, Nobuhiro Hata, Shogo Inamine, Noriaki Sagata, Noritoshi Shirouzu, Nobutaka Mukae, Satoshi O. Suzuki, Hideomi Hamasaki, Ryusuke Hatae, Yuhei Sangatsuda, Yutaka Fujioka, Kosuke Takigawa, Yusuke Funakoshi, Toru Iwaki, Masako Hosoi, Koji Iihara, Masahiro Mizoguchi, Takahiro A. Kato

    Frontiers in Immunology   12   2021年6月

     詳細を見る

    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients’ peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearman’s correlation coefficient = 0.5225, <italic>P &amp;lt;</italic>0.0001). Synchronous upregulation of CD206 expression levels was observed in most patients with glioma (6/9, 66.7%) and almost all patients with glioblastoma (4/5, 80%). Therefore, iMG cells can be used as a minimally invasive tool for monitoring the disease-related immunological state of GAM in various brain diseases, including glioma. CD206 upregulation detected in iMG cells can be used as a surrogate biomarker of glioma.

    DOI: 10.3389/fimmu.2021.670131

    researchmap

  • Personality classification enhances blood metabolome analysis and biotyping for major depressive disorders: two-species investigation 査読

    Daiki Setoyama, Atsuo Yoshino, Masahiro Takamura, Go Okada, Masaaki Iwata, Kyohei Tsunetomi, Masahiro Ohgidani, Nobuki Kuwano, Junichiro Yoshimoto, Yasumasa Okamoto, Shigeto Yamawaki, Shigenobu Kanba, Dongchon Kang, Takahiro A. Kato

    Journal of Affective Disorders   279   20 - 30   2021年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jad.2020.09.118

    Scopus

    PubMed

    researchmap

  • Modulation of inflammatory responses by fractalkine signaling in microglia. 査読 国際誌

    Koichi Inoue, Hiroyuki Morimoto, Masahiro Ohgidani, Takatoshi Ueki

    PloS one   16 ( 5 )   e0252118   2021年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Reactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3CL1). CX3CR1, a FKN receptor, is present in microglial cells, and when FKN is applied before lipopolysaccharide (LPS) administration, LPS-induced inflammatory responses are inhibited, suggesting that the activation of the FKN signal is beneficial. Considering the practical administration for treatment, we investigated the influence of FKN on immunoreactive microglia using murine primary microglia and BV-2, a microglial cell line. The administration of LPS leads to nitric oxide (NO) production. NO was reduced when FKN was administered 4 h after LPS administration without a change in inducible nitric oxide synthase expression. In contrast, morphological changes, migratory activity, and proliferation were not altered by delayed FKN treatment. LPS decreases the CX3CR1 mRNA concentration, and the overexpression of CX3CR1 restores the FKN-mediated decrease in NO. CX3CR1 overexpression decreased the NO production that is mediated by LPS even without the application of FKN. ATP and ethanol also reduced CX3CR1 mRNA concentrations. In conclusion, the delayed FKN administration modified the LPS-induced microglial activation. The FKN signals were attenuated by a reduction in CX3CR1 by some inflammatory stimuli, and this modulated the inflammatory response of microglial cells, at least partially.

    DOI: 10.1371/journal.pone.0252118

    PubMed

    researchmap

  • ProBDNF induces sustained elevation of intracellular Ca<sup>2+</sup> possibly mediated by TRPM7 channels in rodent microglial cells 査読

    Yoshito Mizoguchi, Masahiro Ohgidani, Yoshinori Haraguchi, Toru Murakawa-Hirachi, Takahiro A. Kato, Akira Monji

    GLIA   2021年

     詳細を見る

    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/glia.23996

    Scopus

    researchmap

  • Forskolin rapidly enhances neuron-like morphological change of directly induced-neuronal cells from neurofibromatosis type 1 patients 査読

    Noriaki Sagata, Shin ichi Kano, Masahiro Ohgidani, Shogo Inamine, Yasunari Sakai, Hiroki Kato, Keiji Masuda, Takeshi Nakahara, Makiko Nakahara-Kido, Shouichi Ohga, Masutaka Furue, Akira Sawa, Shigenobu Kanba, Takahiro A. Kato

    Neuropsychopharmacology Reports   40 ( 4 )   396 - 400   2020年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/npr2.12144

    Scopus

    PubMed

    researchmap

  • GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons 査読

    Satoshi Akamine, Sayaka Okuzono, Hiroyuki Yamamoto, Daiki Setoyama, Noriaki Sagata, Masahiro Ohgidani, Takahiro A. Kato, Tohru Ishitani, Hiroki Kato, Keiji Masuda, Yuki Matsushita, Hiroaki Ono, Yoshito Ishizaki, Masafumi Sanefuji, Hirotomo Saitsu, Naomichi Matsumoto, Dongchon Kang, Shigenobu Kanba, Yusaku Nakabeppu, Yasunari Sakai, Shouichi Ohga

    FASEB Journal   34 ( 12 )   16601 - 16621   2020年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1096/fj.202001113R

    Scopus

    PubMed

    researchmap

  • Antidepressant effect of the translocator protein antagonist ONO-2952 on mouse behaviors under chronic social defeat stress 査読 国際誌

    Kanako Nozaki, Hikaru Ito, Masahiro Ohgidani, Yosuke Yamawaki, Ezgi Hatice Sahin, Takashi Kitajima, Seishi Katsumata, Shigeto Yamawaki, Takahiro A. Kato, Hidenori Aizawa

    Neuropharmacology   162   107835 - 107835   2020年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.neuropharm.2019.107835

    Scopus

    PubMed

    researchmap

  • Cuprizone-treated mice, a possible model of schizophrenia, highlighting the simultaneous abnormalities of GABA, serine and glycine in hippocampus 査読

    Eisuke Hayakawa, Masahiro Ohgidani, Yoshinori Fujimura, Shigenobu Kanba, Daisuke Miura, Takahiro A. Kato

    Schizophrenia Research   210   326 - 328   2019年8月

  • Suicide and microglia: Recent findings and future perspectives based on human studies 査読

    Hisaomi Suzuki, Masahiro Ohgidani, Nobuki Kuwano, Fabrice Chrétien, Geoffroy Lorin de la Grandmaison, Mitsumoto Onaya, Itaru Tominaga, Daiki Setoyama, Dongchon Kang, Masaru Mimura, Shigenobu Kanba, Takahiro A. Kato

    Frontiers in Cellular Neuroscience   13   1 - 10   2019年1月

     詳細を見る

    担当区分:筆頭著者  

    DOI: 10.3389/fncel.2019.00031

    Scopus

    researchmap

  • Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study. 査読

    Kuwano N, Kato TA, Mitsuhashi M, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Sakurai T, Kanba S

    Journal of affective disorders   240   88 - 98   2018年11月

  • Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder: An exploratory pilot case-control study. 査読

    Kuwano N, Kato TA, Setoyama D, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Kishimoto J, Kang D, Kanba S

    Journal of affective disorders   231   74 - 82   2018年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jad.2018.01.014

    Scopus

    PubMed

    researchmap

  • p66Shc Signaling Mediates Diabetes-Related Cognitive Decline. 査読 国際誌

    Yohei Minami, Noriyuki Sonoda, Eiichi Hayashida, Hiroaki Makimura, Makoto Ide, Noriko Ikeda, Masahiro Ohgidani, Takahiro A Kato, Yoshihiro Seki, Yasutaka Maeda, Shigenobu Kanba, Ryoichi Takayanagi, Yoshihiro Ogawa, Toyoshi Inoguchi

    Scientific reports   8 ( 1 )   3213 - 3213   2018年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Accumlating evidence have suggested that diabetes mellitus links dementia, notably of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. Several studies have shown oxidative stress (OS) to be one of the major factors in the pathogenesis of diabetic complications. Here we show OS involvement in brain damage in a diabetic animal model that is at least partially mediated through an AD-pathology-independent mechanism apart from amyloid-β accumulation. We investigated the contribution of the p66Shc signaling pathway to diabetes-related cognitive decline using p66Shc knockout (-/-) mice. p66Shc (-/-) mice have less OS in the brain and are resistant to diabetes-induced brain damage. Moreover, p66Shc (-/-) diabetic mice show significantly less cognitive dysfunction and decreased levels of OS and the numbers of microglia. This study postulates a p66Shc-mediated inflammatory cascade leading to OS as a causative pathogenic mechanism in diabetes-associated cognitive impairment that is at least partially mediated through an AD-pathology-independent mechanism.

    DOI: 10.1038/s41598-018-21426-6

    PubMed

    researchmap

  • Blood biomarkers of Hikikomori, a severe social withdrawal syndrome. 査読 国際誌

    Kohei Hayakawa, Takahiro A Kato, Motoki Watabe, Alan R Teo, Hideki Horikawa, Nobuki Kuwano, Norihiro Shimokawa, Mina Sato-Kasai, Hiroaki Kubo, Masahiro Ohgidani, Noriaki Sagata, Hiroyuki Toda, Masaru Tateno, Naotaka Shinfuku, Junji Kishimoto, Shigenobu Kanba

    Scientific reports   8 ( 1 )   2884 - 2884   2018年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori.

    DOI: 10.1038/s41598-018-21260-w

    PubMed

    researchmap

  • Modulating microglial activation as a possible therapeutic target for depression 査読

    Mina Sato-Kasai, Takahiro A. Kato, Masahiro Ohgidani, Hideki Horikawa, Yoshito Mizoguchi, Akira Monji, Shigenobu Kanba

    Understanding Depression   1   209 - 219   2018年1月

     詳細を見る

    掲載種別:論文集(書籍)内論文  

    DOI: 10.1007/978-981-10-6580-4_18

    Scopus

    researchmap

  • Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia 査読

    Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro A. Kato, Akira Monji

    JOURNAL OF NEUROINFLAMMATION   14 ( 1 )   258   2017年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12974-017-1033-0

    Web of Science

    PubMed

    researchmap

  • Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study 査読

    Noriaki Sagata, Takahiro A. Kato, Shin-ichi Kano, Masahiro Ohgidani, Norihiro Shimokawa, Mina Sato-Kasai, Kohei Hayakawa, Nobuki Kuwano, Ashley M. Wilson, Koko Ishizuka, Shiori Kato, Takeshi Nakahara, Makiko Nakahara-Kido, Daiki Setoyama, Yasunari Sakai, Shouichi Ohga, Masutaka Furue, Akira Sawa, Shigenobu Kanba

    SCIENTIFIC REPORTS   7 ( 1 )   13905   2017年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-017-14440-7

    Web of Science

    PubMed

    researchmap

  • Fibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells. 査読

    Ohgidani M, Kato TA, Hosoi M, Tsuda M, Hayakawa K, Hayaki C, Iwaki R, Sagata N, Hashimoto R, Inoue K, Sudo N, Kanba S

    Scientific reports   7 ( 1 )   11882   2017年9月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-017-11506-4

    Web of Science

    PubMed

    researchmap

  • Translational research on neuropsychiatrie disorders: Focusing on microglia hypothesis 査読

    Takahiro A. Kato, Masahiro Ohgidani, Shigenobu Kanba

    Brain and Nerve   69 ( 9 )   1007 - 1015   2017年9月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Scopus

    PubMed

    researchmap

  • Microglia-derived neuregulin expression in psychiatric disorders. 査読 国際誌

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

    Brain, behavior, and immunity   61   375 - 385   2017年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbi.2017.01.003

    Web of Science

    PubMed

    researchmap

  • Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder 査読

    Masahiro Ohgidani, Takahiro A. Kato, Yoshinori Haraguchi, Toshio Matsushima, Yoshito Mizoguchi, Toru Murakawa-Hirachi, Noriaki Sagata, Akira Monji, Shigenobu Kanba

    FRONTIERS IN IMMUNOLOGY   7   676   2017年1月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fimmu.2016.00676

    Web of Science

    PubMed

    researchmap

  • Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis 査読

    Daiki Setoyama, Takahiro A. Kato, Ryota Hashimoto, Hiroshi Kunugi, Kotaro Hattori, Kohei Hayakawa, Mina Sato-Kasai, Norihiro Shimokawa, Sachie Kaneko, Sumiko Yoshida, Yu-ichi Goto, Yuka Yasuda, Hidenaga Yamamori, Masahiro Ohgidani, Noriaki Sagata, Daisuke Miura, Dongchon Kang, Shigenobu Kanba

    PLOS ONE   11 ( 12 )   e0165267   2016年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0165267

    Web of Science

    PubMed

    researchmap

  • Aripiprazole inhibits polyI: C-induced microglial activation possibly via TRPM7 査読

    Mina Sato-Kasai, Takahiro A. Kato, Masahiro Ohgidani, Yoshito Mizoguchi, Noriaki Sagata, Shogo Inamine, Hideki Horikawa, Kohei Hayakawa, Norihiro Shimokawa, Sota Kyuragi, Yoshihiro Seki, Akira Monji, Shigenobu Kanba

    SCHIZOPHRENIA RESEARCH   178 ( 1-3 )   35 - 43   2016年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.schres.2016.08.022

    Web of Science

    PubMed

    researchmap

  • TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice. 査読

    Ohgidani M, Kato TA, Sagata N, Hayakawa K, Shimokawa N, Sato-Kasai M, Kanba S

    Brain, behavior, and immunity   55   17 - 24   2016年7月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbi.2015.08.022

    Web of Science

    PubMed

    researchmap

  • Directly Induced Glial/Neuronal Cells from Human Peripheral Tissues: A Novel Translational Research Tool for Neuropsychiatric Disorders 査読

    Takahiro A. Kato, Masahiro Ohgidani, Noriaki Sagata, Shigenobu Kanba

    Advances in Neuroimmune Biology   6 ( 2 )   95 - 105   2016年

  • Introducing directly induced microglia-like (iMG) cells from fresh human monocytes: a novel translational research tool for psychiatric disorders 査読

    Masahiro Ohgidani, Takahiro A. Kato, Shigenobu Kanba

    FRONTIERS IN CELLULAR NEUROSCIENCE   9   184   2015年5月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fncel.2015.00184

    Web of Science

    PubMed

    researchmap

  • Brain-derived Neurotrophic Factor (BDNF) Induces Sustained Intracellular Ca2+ Elevation through the Up-regulation of Surface Transient Receptor Potential 3 (TRPC3) Channels in Rodent Microglia 査読

    Yoshito Mizoguchi, Takahiro A. Kato, Yoshihiro Seki, Masahiro Ohgidani, Noriaki Sagata, Hideki Horikawa, Yusuke Yamauchi, Mina Sato-Kasai, Kohei Hayakawa, Ryuji Inoue, Shigenobu Kanba, Akira Monji

    JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 26 )   18549 - 18555   2014年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M114.555334

    Web of Science

    PubMed

    researchmap

  • Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease 査読

    Masahiro Ohgidani, Takahiro A. Kato, Daiki Setoyama, Noriaki Sagata, Ryota Hashimoto, Kazue Shigenobu, Tetsuhiko Yoshida, Kohei Hayakawa, Norihiro Shimokawa, Daisuke Miura, Hideo Utsumi, Shigenobu Kanba

    SCIENTIFIC REPORTS   4   4957   2014年5月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep04957

    Web of Science

    PubMed

    researchmap

  • Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys 査読

    Masahiro Ohgidani, Koichi Furugaki, Kentaro Shinkai, Yumi Kunisawa, Keiji Itaka, Kazunori Kataoka, Kenji Nakano

    JOURNAL OF CONTROLLED RELEASE   167 ( 3 )   238 - 247   2013年5月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jconrel.2013.02.006

    Web of Science

    PubMed

    researchmap

  • Residual powders from Shochu distillation remnants induce apoptosis in human hepatoma cells via the caspase-independent pathway 査読

    Masahiro Ohgidani, Yuji Komizu, Koichi Goto, Ryuichi Ueoka

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   114 ( 1 )   104 - 109   2012年7月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jbiosc.2012.02.026

    Web of Science

    PubMed

    researchmap

  • Antimelanogenic and antioxidative effects of residual powders from Shochu distillation remnants 査読

    Masahiro Ohgidani, Yuji Komizu, Koichi Goto, Ryuichi Ueoka

    FOOD CHEMISTRY   132 ( 4 )   2140 - 2143   2012年6月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.foodchem.2011.12.049

    Web of Science

    researchmap

  • Anticancer Effects of Residual Powder from Barley-Shochu Distillation Remnants against the Orthotopic Xenograft Mouse Models of Hepatocellular Carcinoma in Vivo 査読

    Masahiro Ohgidani, Hideaki Ichihara, Koichi Goto, Yoko Matsumoto, Ryuichi Ueoka

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   35 ( 6 )   984 - 987   2012年6月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1248/bpb.35.984

    Web of Science

    PubMed

    researchmap

▼全件表示

MISC

▼全件表示

講演・口頭発表等

  • グリア細胞からアプローチする生物学的精神医学研究 招待

    扇谷 昌宏

    第21回日本うつ病学会総会  2024年 

     詳細を見る

  • ヒト末梢血誘導型ミクログリア細胞技術を用いた慢性疼痛研究 招待

    扇谷 昌宏

    第62回日本心身医学会総会学術講演会  2021年 

     詳細を見る

  • Introducing our psychiatric translational reserch system to clarify the pathological neuron-glia interaction using human induced microglia-like (iMG) cells and induced neuronal (iN) cells. 招待

    Masahiro Ohgidani

    6th Congress of Asian College of Neuropsychopharmacology  2019年10月 

     詳細を見る

  • ヒト血液由来ミクログリア様細胞を用いた線維筋痛症の客観的バイオマーカー開発 招待

    扇谷昌宏, 加藤隆弘

    第35回日本ストレス学会学術総会  2019年 

     詳細を見る

産業財産権

受賞

  • 優秀論文賞

    2024年11月   日本動物実験代替法学会  

    扇谷 昌宏

     詳細を見る

  • JSNP Excellent Presentation Award for CINP 2024

    2024年5月   Japanese Society of Neuropsychhopharmacology   Direct induction of microglia-like cells from human monocytes: A novel cellular tool for translational research of neuropsychoiatric disorders

    Masahiro Ohgidani

     詳細を見る

  • 優秀発表賞

    2019年10月   日本神経精神薬理学会   第49回日本精神神経薬理学会年会

    扇谷昌宏

     詳細を見る

  • 若手優秀発表賞

    2019年7月   日本神経化学会   第62回日本神経化学会、第42回日本神経科学会合同大会

    扇谷昌宏

     詳細を見る

  • 奨励賞

    2018年6月   日本生物学的精神医学会   第41回日本生物学的精神医学会

    扇谷昌宏

     詳細を見る

  • 優秀演題賞

    2017年11月   日本動物実験代替法学会   日本動物実験代替法学会第31回大会

    扇谷昌宏

     詳細を見る

  • KJYPA award

    2016年11月   Korea-Japan Young Psychiatrists’ Conference   18th Korea-Japan Young Psychiatrists’ Conference.

    Masahiro Ohgidani

     詳細を見る

  • 学会年会賞

    2015年7月   日本神経精神薬理学会   第46回日本神経精神薬理学会年会

    扇谷昌宏

     詳細を見る

  • 優秀賞

    2010年12月   大学発ベンチャービジネスプランコンテスト実行委員会   第10回大学発ベンチャービジネスプランコンテスト

    扇谷昌宏

     詳細を見る

  • 奨励賞

    2009年11月   熊本県   夢挑戦ビジネス大賞2009 in くまもと

    扇谷昌宏

     詳細を見る

▼全件表示

共同研究・競争的資金等の研究課題

  • ヒトの末梢及び中枢免疫系から明らかにする加齢の正体と加齢性疾患治療への応用

    研究課題/領域番号:24K22242  2024年6月 - 2026年3月

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    扇谷 昌宏

      詳細を見る

    担当区分:研究代表者 

    researchmap

  • 精神神経疾患におけるミクログリア活性化とは何か?ヒト細胞を用いた疾患横断的研究

    研究課題/領域番号:23K24261  2024年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    扇谷 昌宏, 山崎 亮, 加藤 隆弘

      詳細を見る

    担当区分:研究代表者 

    researchmap

  • ヒト末梢血誘導型ミクログリア細胞(iMG)技術を用いた認知症の病態機序解析ならびに臨床症状と細胞機能との相互解析による新規治療標的の探索

    2022年4月 - 2025年3月

    日本医療研究開発機構(AMED)  認知症研究開発事業 

      詳細を見る

    担当区分:研究代表者 

    researchmap

  • 精神神経疾患におけるミクログリア活性化とは何か?ヒト細胞を用いた疾患横断的研究

    研究課題/領域番号:22H03000  2022年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    扇谷 昌宏, 山崎 亮, 加藤 隆弘

      詳細を見る

    担当区分:研究代表者 

    脳にはニューロン(神経細胞)以外にも様々な細胞が存在しており、それらの細胞が疾患と深く関わっていることが近年明らかにされている。特に、脳内で唯一の免疫細胞であるミクログリアは、他の細胞と由来や性質が大きく異なり、疾患への関与が非常に注目されている。
    近年、精神神経疾患において、ミクログリアが活性化していることは紛れもない事実として認識されている。しかしながら、非常に多様な現象が十把一絡げに“活性化”の一言で片付けられている。そのため、各疾患においてミクログリアの何が?どのように?活性化しているのかをヒトのレベルで疾患横断的に詳細に解析し、分類した研究は未だ無い。
    本研究は、申請者が開発したヒト末梢血誘導型ミクログリア細胞技術を用いて、患者由来のミクログリアを分子・細胞機能レベルで詳細に解析し、各疾患に特異的な活性化の分類を行うことを目的としている。
    疾患横断的にミクログリアの活性化を分類することで、精神神経疾患とミクログリアの関係を俯瞰的に捉えることが可能となる。そうして本研究は、未だ謎が多い精神神経疾患の本質にミクログリアという切り口で迫ろうとするものである。
    本年度は、実験条件の確立およびリクルートを行った。いくつかの疾患において健常群と異なる現象を確認することができた。現在、症例の追加や追加実験を実施中である。

    researchmap

  • 持続式陽圧呼吸療法による抑うつ症状改善のメカニズムの探索

    研究課題/領域番号:21K07523  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    野上 耕二郎, 野出 孝一, 白木 綾, 西原 正志, 扇谷 昌宏, 門司 晃, 溝口 義人, 村川 徹, 立石 洋, 國武 裕, 松島 淳

      詳細を見る

    担当区分:研究分担者 

    配分額:4,290,000円 ( 直接経費:3,300,000円 、 間接経費:990,000円 )

    2021年4月から11月にかけて、研究室における実験設備、試薬を購入し、iMG(induced microglial-like cell)の作製手技を共同研究者より習得し、その後も研究代表者を含む研究者でiMG単離、誘導の手技を再確認した。2021年7月29日に佐賀大学医学部附属病院臨床研究倫理審査委員会において、循環器内科睡眠時無呼吸外来で精神科薬の内服がない成人で睡眠時無呼吸症候群が疑われる患者に対して、精神科病棟に1泊2日で入院の上、最大70mlの採血、唾液3mlの採取、頭部MRI検査、脳波検査、睡眠ポリグラフ検査、各種心理検査を行い、CPAP適応の可否を判断し、適応となった患者に対しては3か月CPAPを行い、その後再度精神科病棟に検査入院を行う倫理申請を行い、承認された。その後、2021年12月に1例目の患者、2022年3月31日までに2例目の患者が入院し、1例目の患者に関してはCPAP後の入院検査まで修了。また、2022年3月31日までにさらに2回倫理委員会変更申請を行い、多施設研究、外部への検査委託も追加し、多施設研究においては、九州大学において定量脳波解析と、メタボローム解析を依頼し、提携した。

    researchmap

  • CCL11による大脳の老化促進仮説に着目した統合失調症の認知機能障害の病態解明

    研究課題/領域番号:21H02845  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    久住 一郎, 石川 修平, 橋本 直樹, 扇谷 昌宏, 豊巻 敦人, 古賀 農人

      詳細を見る

    担当区分:研究分担者 

    researchmap

  • リキッドバイオプシーによる免疫ゲノム解析に基づくグリオーマ免疫環境多様性の解明

    研究課題/領域番号:21H03044  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    溝口 昌弘, 加藤 隆弘, 秦 暢宏, 空閑 太亮, 三月田 祐平, 扇谷 昌宏

      詳細を見る

    担当区分:研究分担者 

    配分額:17,550,000円 ( 直接経費:13,500,000円 、 間接経費:4,050,000円 )

    WHO2021分子診断アルゴリズムの確立:
    1年間で47例のグリオーマ症例に対し摘出術をおこない、従来のHRM法に加えMLPA法による解析を検討した。統合診断の結果、Glioblastoma 17例、Astrocytoma IDH-mut 13例 、Oligodendroglioma 1p19q codel 8例 、Diffuse midline glioma H3K27-altered 2例、その他7例となった。 MLPA法によりAstrocytoma IDH-mutにおいて CDKN2A/B欠失を確定し、2例をgrade4と診断した。さらに後方視的に360例に対しMLPA法による解析を検証し、WHO2021改訂に対応できる解析アルゴリズムを構築した。
    iMG細胞誘導および腫瘍原発巣の微小免疫環境の評価:
    11例のグリオーマ症例に対し、新たに末梢血よりiMG細胞を培養、誘導した。のべ33例の脳疾患患者(グリオーマ20例、その他13例)の病変周囲組織と同一患者の末梢血由来iMG細胞を解析した。我々が同定したiMG細胞におけるCD206発現の解析を継続、蓄積した。脳内ミクログリア、iMG細胞の貪食能を評価をし、グリオーマ8症例を含む脳外科疾患11例において脳内ミクログリアとiMG細胞の貪食能に正の相関を認めた。
    脳腫瘍症例体液(血液・髄液)解析:
    髄液を対象としたリキッドバイオプシーを23例のグリオーマ症例におこなった。IDH1、H3F3A、BRAF、pTERTについてDigital PCR解析を行った。2例でIDH 1 R132H mut、1例で pTERT C228T、1例で pTERT C250T、1例でH3K27M mutを正確に判定することができた。脳幹部の腫瘍2例のうち、1例にH3F3A遺伝子変異を認めた。

    researchmap

  • ヒト末梢血誘導型ミクログリア細胞技術を用いた食品の神経毒性評価システムの開発

    2020年4月 - 2023年3月

    厚生労働省  厚生労働科学研究費補助金 

      詳細を見る

    担当区分:研究代表者 

    researchmap

  • 重篤な精神神経症状を呈するミクログリア病(HDLS)の病態機序解明と治療法の探索

    研究課題/領域番号:19K17065  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    扇谷 昌宏

      詳細を見る

    配分額:4,160,000円 ( 直接経費:3,200,000円 、 間接経費:960,000円 )

    脳細胞の一種であるミクログリアは脳内で様々な役割を担っており、その機能異常は重篤な精神神経症状を呈するミクログリア病を引き起こす。しかし、ミクログリア病という病名がついているにもかかわらずミクログリアの何が?どのように?異常なのか全く明らかになっておらず、病態機序および治療法も確立されていない。
    本研究は、申請者が開発したヒト末梢血誘導型ミクログリア様細胞技術を用いて、ミクログリアの機能異常を細胞レベルで解析し、ミクログリア病の病態機序の解明と新規治療法の探索を行うことを目的としている。
    本年度は、実際のHDLS患者から血液を採取し、ミクログリア様細胞(iMG細胞)の作製を行うことができた。表現系の解析から、健常者と比べて明らかに違いがあることを発見した。
    加えて、マウス脳から採取したプライマリーミクログリア細胞とsiRNAを用いて作製したHDLSモデル細胞において、臨床検体と同様の変化を確認した。
    現在、そのメカニズムと病態への寄与を検討している。

    researchmap

  • せん妄群と非せん妄群における血中の単球から誘導したミクログリア様細胞の動態比較

    研究課題/領域番号:19K08022  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    村川 徹, 門司 晃, 阪本 雄一郎, 溝口 義人, 扇谷 昌宏

      詳細を見る

    担当区分:研究分担者 

    配分額:4,290,000円 ( 直接経費:3,300,000円 、 間接経費:990,000円 )

    2019年4月から8月にかけて、研究室における実験設備、試薬を購入し、iMG(induced microglial-like cell)の作製手技を共同研究者より習得し、その後も研究代表者を含む研究者でiMG単離、誘導の手技を再確認した。実験設備、試薬類が2019年度の費用では購入できなかったため、研究費の前倒し申請を行い、承認され、2019年度において設備及び試薬類を3年間で遂行するにあたり問題ないまでに準備、整備した。2019年11月5日に佐賀大学医学部附属病院臨床研究倫理審査委員会において、佐賀大学医学部附属病院救命救急センターに入院した、認知症を有さない70代のせん妄を発症した患者に限り、せん妄をDRS-R98とMMSE(Mini mental State Examination)において評価したうえで、最大50mlの採血を行いiMG誘導を行う倫理申請を行い、承認された。またそれ以前に、DRS-R98作成者より使用許可を得た。2019年4月から2020年1月までは毎月県内のリエゾン医を有する精神科病院のコンサルト担当で集まり、せん妄の評価の方法を統一する話し合いを行った。DRS-R98を使用して大規模にせん妄研究を行っているせん妄ガイドライン作成者に連絡を取り、改めてせん妄評価を統一した。その後70代で認知症のないせん妄患者の救命救急センター入院がなく、症例が集まらなかった。そのため2020年3月に佐賀大学医学部附属病院臨床研究倫理審査委員会に対象症例とコントロール群ともに、70代だけではなく、50代以上90歳未満へ広げる変更を申請し、また、症例を集める期間とそのデータを解析する期間に関しても、本実験の終了日にまで延長する変更申請を行った。変更申請は3月19日に承認された。

    researchmap

  • ヒト末梢血誘導型ミクログリア様細胞を用いた慢性疲労症候群の客観的評価系の確立

    研究課題/領域番号:17K19915  2017年6月 - 2019年3月

    日本学術振興会  科学研究費助成事業 挑戦的研究(萌芽)  挑戦的研究(萌芽)

    扇谷 昌宏

      詳細を見る

    担当区分:研究代表者 

    配分額:6,370,000円 ( 直接経費:4,900,000円 、 間接経費:1,470,000円 )

    本研究では、申請者の開発した末梢血誘導型ミクログリア様細胞技術を用いて、慢性疲労症候群におけるミクログリアの関与と客観的評価法の開発を目的に研究を実施した。
    慢性疲労症候群と類似した症状を示す線維筋痛症患者群において、ATP刺激後ではTNF-αの遺伝子発現が有意に増大していた。さらに興味深いことに、不安・抑うつの重症度(HAD)とTNF-α遺伝子の発現量との間に正の相関関係を認めた。これらの知見は、患者群における精神症状(抑うつ・不安)及びQOLがミクログリア由来のTNF-αによってコントロールされている可能性を示唆している。

    researchmap

  • ヒト体細胞由来ミクログリア作製法の確立と精神疾患研究への応用

    研究課題/領域番号:26860933  2014年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    扇谷 昌宏

      詳細を見る

    担当区分:研究代表者 

    配分額:3,770,000円 ( 直接経費:2,900,000円 、 間接経費:870,000円 )

    ・ヒト末梢血単球からミクログリア様細胞を作製する手法を確立した。
    ・精神疾患を含むミクログリア病において、細胞機能の異常が見られた。
    ・本技術は今後のミクログリア研究に有益なものとなる可能性が示唆された。

    researchmap

▼全件表示