Functional analysis of TLR4-activated long-lived microglia and their neuroprotective effects.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hiroshima University
• Principal Investigator: HIDE IZUMI 広島大学, 医歯薬保建学研究院(医), 助教 (20253073)
• Co-Investigator(Kenkyū-buntansha): SAKAI Norio 広島大学, 大学院医歯薬保建学研究院, 教授 (70263407)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ミクログリア / トル様受容体4 / 生存 / 死細胞貪食 / 神経保護

Outline of Final Research Achievements

Toll-like receptor 4 activation by lipopolysaccharide (LPS) induced both death and survival in rat primary cultured microglia. Here, we investigated the mechanism of survival and purinergic modulation of dead cell phagocytosis and cytokine production in TLR4-activated microglia. LPS stimulation drastically induced the production of GM-CSF and up-regulated GM-CSF receptor signaling in surviving microglia. In addition, LPS-stimulated surviving microglia became motile and actively engulfed dead cells possibly through up-regulated P2Y2 receptors. Furthermore, Adenosine A2a receptors up-regulated by LPS stimulation suppressed TNF production. Purinergic activation promoted a marked elevation of protective cytokines such as activin-A. LPS-stimulated microglia protected neuronal cells in co-culture system. Together, TLR-4-activated long-lived microglia produce GM-CSF as an autocrine survival factor and may acquire protective phenotype through up-regulation of specific purinergic receptors.

Free Research Field

神経薬理学、神経科学