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2021 Fiscal Year Final Research Report

Development of preventive method for stroke sequelae targeting zinc-mediated glial interaction

Research Project

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Project/Area Number 19K09510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionKochi University

Principal Investigator

Higashi Youichirou  高知大学, 教育研究部医療学系基礎医学部門, 講師 (80380062)

Co-Investigator(Kenkyū-buntansha) 上羽 哲也  高知大学, 教育研究部医療学系臨床医学部門, 教授 (00314203)
清水 孝洋  高知大学, 教育研究部医療学系基礎医学部門, 准教授 (00363276)
八幡 俊男  高知大学, 教育研究部医療学系臨床医学部門, 助教 (40380323)
齊藤 源顕  高知大学, 教育研究部医療学系基礎医学部門, 教授 (60273893)
清水 翔吾  高知大学, 教育研究部医療学系基礎医学部門, 助教 (90721853)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywordsミクログリア / アストロサイト / 亜鉛 / 脳卒中 / 脳卒中後遺症
Outline of Final Research Achievements

Glial cells such as microglia (M.glia) and astrocytes (Astro.) play an active role in various pathological conditions including stroke via communications between these glial cells. We examined whether the zinc-enhanced inflammatory M1 phenotype of M.glia affects the Astro. engulfing activity. M.glia-conditioned medium (MCM) from lipopolysaccharide-induced M1 M.glia increased engulfment activity of Astro.. This increased activity was suppressed when MCM from LPS-induced M1 M.glia pretreated with ZnCl2 was applied to Astro., which was further abolished by the intracellular zinc chelator and reactive oxygen species (ROS) scavenger. These findings suggest that zinc-enhanced inflammatory M1 phenotype of M.glia may release soluble factors through intracellular zinc accumulation and ROS generation, which abolishes the ability of M1 M.glia to increase the Astro. engulfing activity.

Free Research Field

脳神経薬理学

Academic Significance and Societal Importance of the Research Achievements

脳卒中後の認知障害や気分障害は発症頻度が比較的高く早急な対策が必要である。このような脳卒中後遺症は、アストロサイトやミクログリアなどグリア細胞の関与も指摘されている。しかし、その詳細な機序は十分に理解されていない。今回得られた研究成果は世界で初めての知見であり、これらは未だ存在しないグリア細胞間の機能制御機構を標的とした脳卒中後遺症の発症及び重篤化を阻止する有効な予防法の開発に繋げることが出来る意義深い知見である。

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Published: 2023-01-30  

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