Roles of lipid signaling and remodeling in nerve injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03395
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Nagoya University
• Principal Investigator: Kiyama Hiroshi 名古屋大学, 医学系研究科, 教授 (00192021)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 軸索再生 / 脂質 / 神経変性 / 神経再生

Outline of Final Research Achievements

We have been examining molecular mechanisms underlying neuronal degeneration and regeneration after nerve injury. In our gene screening we have identified several molecules associated with lipid dynamics. Our previous GPCR screening revealed several orphan receptors were expressed by glial cells in response to nerve injury. Recently those orphan GPCRs were deorphanized and found that some of them were associated with intercellular lipid signaling. In this study we have examined the functional significances of phosphatidylserine receptor GPR34, and found the GPR34 mediated signal is associated with neuropathic pain.
Nerve injury induced characteristic changes of membrane of injured neurons. The remodeling of lipid composition would be necessary for axon regeneration. Furthermore, lipid remodeling in glial cells was found to be critical for the changes of microglial morphology. We also found that the lipid mediated signaling is critical in phagocytosis by microglia and astrocyte.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

運動神経軸索障害は著しい運動障害だけでなく、神経障害性疼痛など難治性の疼痛の原因となる。損傷神経の修復による運動機能の修復や神経障害性疼痛からの開放に至る研究は、QOLの観点から重要な課題である。本研究では損傷修復の修復過程に脂質のリモデリングや脂質を介する神経・グリア細胞間情報伝達が重要であることを明らかにした。損傷神経修復過程のコレステロールやリン脂質の局在変化やグリアにおける脂質受容体を介する応答は、今後の治療の標的となりうることが動物を用いた基礎研究で明らかとなった。