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dc.contributor.authorMiyanohara, Jun-
dc.contributor.authorKakae, Masashi-
dc.contributor.authorNagayasu, Kazuki-
dc.contributor.authorNakagawa, Takayuki-
dc.contributor.authorMori, Yasuo-
dc.contributor.authorArai, Ken-
dc.contributor.authorShirakawa, Hisashi-
dc.contributor.authorKaneko, Shuji-
dc.contributor.alternative宮之原, 遵-
dc.contributor.alternative抱, 将史-
dc.contributor.alternative永安, 一樹-
dc.contributor.alternative中川, 貴之-
dc.contributor.alternative森, 泰生-
dc.contributor.alternative荒井, 健-
dc.contributor.alternative白川, 久志-
dc.contributor.alternative金子, 周司-
dc.date.accessioned2019-05-23T08:04:33Z-
dc.date.available2019-05-23T08:04:33Z-
dc.date.issued2018-04-04-
dc.identifier.issn0270-6474-
dc.identifier.urihttp://hdl.handle.net/2433/241611-
dc.description脳の血流低下が認知機能障害を引き起こす --脳の免疫細胞「ミクログリア」による脳内炎症と白質傷害が原因か--. 京都大学プレスリリース. 2018-03-09.-
dc.description.abstractChronic cerebral hypoperfusion is a characteristic seen in widespread CNS diseases, including neurodegenerative and mental disorders, and is commonly accompanied by cognitive impairment. Recently, several studies demonstrated that chronic cerebral hypoperfusion can induce the excessive inflammatory responses that precede neuronal dysfunction; however, the precise mechanism of cognitive impairment due to chronic cerebral hypoperfusion remains unknown. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable channel that is abundantly expressed in immune cells and is involved in aggravation of inflammatory responses. Therefore, we investigated the pathophysiological role of TRPM2 in a mouse chronic cerebral hypoperfusion model with bilateral common carotid artery stenosis (BCAS). When male mice were subjected to BCAS, cognitive dysfunction and white matter injury at day 28 were significantly improved in TRPM2-knockout (TRPM2-KO) mice compared with wild-type (WT) mice, whereas hippocampal damage was not observed. There were no differences in blood-brain barrier breakdown and H2O2 production between the two genotypes at 14 and 28 days after BCAS. Cytokine production was significantly suppressed in BCAS-operated TRPM2-KO mice compared with WT mice at day 28. In addition, the number of Iba1-positive cells gradually decreased from day 14. Moreover, daily treatment with minocycline significantly improved cognitive perturbation. Surgical techniques using bone marrow chimeric mice revealed that activated Iba1-positive cells in white matter could be brain-resident microglia, not peripheral macrophages. Together, these findings suggest that microglia contribute to the aggravation of cognitive impairment by chronic cerebral hypoperfusion, and that TRPM2 may be a potential target for chronic cerebral hypoperfusion-related disorders.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherSociety for Neuroscience-
dc.rights© 2018 Authors. This paper was deposited under 'AUTHOR LICENSE POLICY'. (http://www.jneurosci.org/content/rights-permissions)-
dc.subjectcerebral hypoperfusion-
dc.subjectcognitive impairment-
dc.subjectcytokine-
dc.subjectmicroglia-
dc.subjectTRPM2-
dc.subjectwhite matter injury-
dc.titleTRPM2 channel aggravates CNS inflammation and cognitive impairment via activation of microglia in chronic cerebral hypoperfusion.-
dc.type.niitypeJournal Article-
dc.identifier.jtitleThe Journal of neuroscience : the official journal of the Society for Neuroscience-
dc.identifier.volume38-
dc.identifier.issue14-
dc.identifier.spage3520-
dc.identifier.epage3533-
dc.relation.doi10.1523/JNEUROSCI.2451-17.2018-
dc.textversionpublisher-
dc.addressDepartment of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University-
dc.addressDepartment of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University-
dc.addressDepartment of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University-
dc.addressDepartment of Clinical Pharmacology and Therapeutics, Kyoto University-
dc.addressDepartment of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University-
dc.addressNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School-
dc.addressDepartment of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University-
dc.addressDepartment of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University-
dc.address.alternative京都大学大学院薬学研究科-
dc.address.alternative京都大学大学院薬学研究科-
dc.address.alternative京都大学大学院薬学研究科-
dc.address.alternative京都大学医学部附属病院薬剤部-
dc.address.alternative京都大学大学院工学研究科-
dc.address.alternative米国ハーバード大学医学部・マサチューセッツ総合病院-
dc.address.alternative京都大学大学院薬学研究科-
dc.address.alternative京都大学大学院薬学研究科-
dc.identifier.pmid29507145-
dc.identifier.kaken25460098 / 24390016-
dc.relation.urlhttp://www.kyoto-u.ac.jp/ja/research/research_results/2017/180309_1.html-
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