2020 Fiscal Year Final Research Report
Role of proton-sensing G-protein-coupled receptors in the regulation of microglia and microvessel endothelial cell function in the brain stroke in a mouse ischemia reperfusion model.
| Project/Area Number |
18K07362
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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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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Gunma University |
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Principal Investigator |
Sato Koichi 群馬大学, 生体調節研究所, 准教授 (00302498)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | プロトン感知性受容体 / G蛋白共役型受容体 / 脳虚血 / ミクログリア / 微小血管内皮細胞 / 脳内炎症 / 細胞死 / 酸性pH |
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| Outline of Final Research Achievements |
Extracellular acidic pH of ~6.0 has been shown to take place with brain ischemia. However, their mechanisms for signaling an acidic pH in a cerebral injury during ischemia have been poorly elucidated. Proton-sensing OGR1 family G-protein coupled receptors (GPCRs, including OGR1, GPR4, and TDAG8) have been shown to be expressed in central nervous system. This study has focused on the roles of proton-sensing GPCRs in the brain injury in a mouse ischemia reperfusion model. Our results suggested that acidic pH/TDAG8 functions protectively for cerebral infarction by the ischemia model possibly due to the mechanism involving inhibitory actions against microglia function. We also found the involvement of acidic pH/GPR4 in the expression of adhesion molecules in endothelial cells. Thus, although further studies are necessary to clarify the roles of proton-sensing GPCRs in ischemic brain functions, they may help to identify the therapeutic targets for a brain injury accompanied by acidosis.
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| Free Research Field |
細胞生物学、病態神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では虚血性神経性疾患で報告されている低pH環境変動が中枢神経系細胞群の活性制御を介して神経機能に何らかの作用を及ぼし、脳内恒常性の破綻に関わっているのではないかという仮説を実証しようとしたものである。微小環境因子としてのpH変動は中枢神経系を含む様々な炎症性疾患で生じていると想定されており、このような環境変化を感知する受容体分子の究明は炎症性疾患の新しい治療戦略の構築に寄与すると期待される。また、本研究の成果は細胞外pH変化による多彩な生物作用の分子基盤となる。
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