Microglial function in hypoxic-ischemic encephalopathy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: KOUCHI Zen 愛知県心身障害者コロニー発達障害研究所, 病理学部, 研究員 (70322485)
• Co-Investigator(Kenkyū-buntansha): HOSOKAWA Masanori 愛知県心身障害者コロニー・発達障害研究所, 病理学部, 部長(兼任) (00127135) ; SHIMADA Atsuyoshi 愛知県心身障害者コロニー・発達障害研究所, 病理学部, 室長(兼任) (50311444) ; ENOKIDO Yasushi 愛知県心身障害者コロニー・発達障害研究所, 病理学部, 室長 (90263326) ; CHIBA Yoichi 元愛知県心身障害者コロニー・発達障害研究所, 病理学部, 主任研究員
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: microglia / LPS / cytokine / monoacylglycerol lipase / ABHD12

Outline of Final Research Achievements

It has been known that monoacylglycerol lipase (MAGL) is involved in wiring process of neural network in brain development, however, its pathological function in inflammatory condition remains unknown. We found that MAGL transcription was downregulated in neonatal brain subjected to hypoxic/ischemic stress and primary microglia treated with lipopolysaccharide (LPS). Microglial MAGL was transcriptionally regulated by Stat6 and its protein was rapidly degraded by proteasome in steady state. LPS treatment inhibited its degradation, resulting in its stabilization in microglia. Intrinsic MAGL was not prerequisite for LPS-dependent induction of several inflammatory cytokines such as IL6 in normoxic or hypoxic conditions, whereas it promoted phagocytosis mediated by Fcγ receptor in microglia.

Free Research Field

細胞生物学、生化学、病理学