2015 Fiscal Year Final Research Report
Modulation of microglial activation by regulating cation channels and its application to disease association
| Project/Area Number |
25460098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KANEKO SHUJI 京都大学, 大学院・薬学研究科, 教授 (60177516)
NAKAGAWA TAKAYUKI 京都大学, 大学院・医学研究科, 准教授 (30303845)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | ミクログリア / TRPV1 / TRPM2 / 遊走 / 一酸化窒素 / 活性酸素種 / 脳虚血傷害 / 多発性硬化症 |
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| Outline of Final Research Achievements |
Microglia, the resident immune cells in the brain, maintain brain homeostasis at a resting state by surveying the environment and engulfing debris. However, in some pathological conditions, microglia can produce neurotoxic factors. Inflammation-induced Ca2+ signaling is thought to underlie this abnormal activation of microglia, but the mechanisms and the molecular identities are still obscure. Here, we focus on the pathophysiological roles of TRP channels in CNS diseases. In vitro and in vivo experiments demonstrate that 1) TRPM2 contributes to excessive production of nitric oxide in microglia, 2) TRPM2-KO improves the neurological outcomes of mouse multiple sclerosis model, 3) Activation of mitochondrial TRPV1 contributes to microglial migration, 4) TRPV1-KO attenuates neurological deficiency in mouse cerebral ischemia model, suggesting that the above-mentioned TRP channels are potential therapeutic targets to regulate microglial activation and neuroinflammation in CNS diseases.
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| Free Research Field |
中枢神経薬理
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