Controlling bi-directional Notch-Delta signalling in hippocampal neural stem cells to enhance the self-renewal and the neurogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21913
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: National Institute of Health Sciences
• Principal Investigator: OKUBO YUSUKE 国立医薬品食品衛生研究所, 毒性部, 主任研究官 (80596247)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: Notchシグナル / Deltaシグナル / 神経幹細胞 / 神経新生

Outline of Final Research Achievements

The activation of neurogenesis in the hippocampus is postulated to provide therapeutic strategies for memory impairments. However, a significant concern is the potential induction of senescence and depletion in neural stem cells associated with such stimulation. In our study, we first use approaches involving multivalent Delta proteins to facilitate the self-renewal of neural stem cells by activating Notch signaling. Subsequently, we enhance neurogenesis via Delta signaling, activated using an adeno-associated virus. In this research, we conducted an examination of Notch- and Delta- signaling activation approaches using cellular models. We also established techniques for detecting these activation approaches, as well as the self-renewal of neural stem cells and neurogenesis in the hippocampus of rats.

Free Research Field

幹細胞工学

Academic Significance and Societal Importance of the Research Achievements

ヒトの記憶障害やうつ病など社会的に治療の要請が高い疾患と海馬神経新生の低下との関連が指摘されており、神経新生を賦活化することでその治療につながると期待されている。一方で、過剰な神経刺激による神経新生の促進は神経幹細胞を減少させることが報告されており、適切な治療法の開発には安全性も考慮する必要がある。本研究において、副作用を抑えた神経新生の賦活化法を開発するための基盤技術を確立した。今後、これらの技術を用いた治療法の開発が期待される。