Elucidation of the molecular basis of neurogenesis by regulation of fatty acid composition

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K19669
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Tsukuba
• Principal Investigator: OHNO Hiroshi 筑波大学, 医学医療系, 助教 (20847909)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 脂肪酸 / スフィンゴ脂質 / 神経幹細胞

Outline of Final Research Achievements

In this study, we aimed to elucidate the molecular mechanisms underlying the impaired neurogenesis found in CNS-specific Elovl6-deficient (BKO) mice. Lipid metabolomics analysis of neural stem cells revealed that BKO-derived neural stem cells contain significant differences in lipids, which are important for the composition of nanodomains in the plasma membrane, and that inhibitors of specific lipid molecules restored their self-renewal capacity. In addition, when the fractionation of nanodomains was assessed, the fractionation of nanodomains was altered in BKO-derived neural stem cells and was restored to normal by inhibitors of lipid species. Thus, the results suggest that Elovl6 may be responsible for signal transduction reconstitution by regulating the organization of plasma membrane nanodomains.

Free Research Field

脂質代謝

Academic Significance and Societal Importance of the Research Achievements

認知機能の低下は現代社会における大きな問題の１つである。本研究において神経新生の制御メカニズムを分子レベルで明らかにすることは、認知機能の低下に対する脂質の質の重要性を明らかにしたという点で意義がある。さらに、脂肪酸組成の制御による認知機能維持機構の解明は、これまで特定の神経やその受容体を標的とした精神・神経疾患の治療とは大きく異なり、より広範で副作用の少ない新規治療法の開発に貢献できる可能性が示唆される。