The functional significance of ASPM, responsible gene for human microcephaly, in the activation of adult neural stem cells - a new approach to brain anti-aging

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K01722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tando So 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80423870)
• Co-Investigator(Kenkyū-buntansha): 伊東 恭子 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80243301)
• Research Collaborator: Fujimori Akira
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 加齢・老化 / ASPM / 神経幹細胞 / MRI / 行動表現型

Outline of Final Research Achievements

The aim of our study is to elucidate the role of ASPM gene in brain maturation and the hippocampal adult neurogenesis with aging.
MRI analysis showed that the fractional anisotropy (FA) values were　significantly lower in both the cortex and white matter, and developmental changes in the FA values were less remarkable in the Aspm KO mice as compared with the controls. Histopathological analyses revealed that the ratios of the horizontal to vertical neurites were altered in the KO mice, suggesting that abnormal neurite outgrowth and differentiation in Aspm KO mice. Next, we examined adult hippocampal neurogenesis with aging. The number of BrdU- and DCX-positive cells in the dentate gyrus showed a significant decrease with age in Aspm KO mice as compared to the controls. However, the number of nestin-positive cells was not changed, suggesting that Aspm might be involved in the differentiation process of hippocampal neural stem cells to young neurons with aging.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

これまで、小頭症原因遺伝子ASPMの生後の脳発達や加齢における機能的意義については、殆ど解析されてこなかった。今回、我々は、ASPMが脳成熟過程における神経線維の分化や伸長に関与することを明らかにした。また、老化Aspm KOマウスにおける海馬神経細胞新生の低下を見出した。ASPMが、脳形成期のみならず、生後の脳成熟や老化にも深く関与することを世界に先駆けて示した成果である。今後、ASPM遺伝子活性化により神経線維の構造的異常や加齢に伴う神経細胞新生低下の改善が可能となれば、小頭症患者の脳機能改善への道を開く意義のある結果と考えられる。