Role of proton-sensing G protein-coupled receptors on microglial activation and neuronal cell survival in a mouse ischemia reperfusion model.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06767
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Gunma University
• Principal Investigator: SATO Koichi 群馬大学, 生体調節研究所, 准教授 (00302498)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 脳虚血 / 脳内炎症 / ミクログリア / 炎症性サイトカイン / 酸性ストレス / 細胞死 / G蛋白共役型受容体 / pH感知性受容体

Outline of Final Research Achievements

Extracellular acidic pH of ~6.5 has been shown to take place with ischemia and neurodegenerative. However, the mechanisms underlying acidic pH-induced actions are poorly understood. Proton-sensing OGR1 family G-protein coupled receptors (GPCRs, including OGR1, GPR4, and TDAG8) have been shown to be expressed in brain. This study has focused on the roles of proton-sensing GPCRs in the brain injury in a mouse ischemia reperfusion model. We also analyzed roles of proton-sensing GPCRs in mouse microglia and neuronal cells in acidic pH medium. Our results suggested that acidic pH /TDAG8 functions protectively for cerebral infarction by the mouse ischemia model possibly due to the mechanism involving inhibitory actions against microglia function. And also we showed the involvement of OGR1 and/or GPR4 in the acidic pH regulation of neuronal cell functions. Thus, the elucidation of acidic pH actions may provide therapeutic targets of neurodegenerative disorders such as ischemic stroke.

Free Research Field

神経機能学