Development of cerebral infarction regeneration method that combines neurogenesis and angiogenesis with new guidance factors

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yamagishi Satoru 浜松医科大学, 医学部, 准教授 (40372362)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: Netrin-5 / 神経新生 / 吻側移動流 / DCX / ガイダンス分子

Outline of Final Research Achievements

The axon guidance molecule Netrin-5, which we reported in 2015, is strongly expressed in neurogenesis related areas, but its function was unknown. In this research project, we focused on the function of Netrin-5 in cerebral infarction, but did not obtain the expected results. However, analysis of Netrin-5 knockout mice revealed abnormal neurogenesis. The cell division cycle in the SVZ was longer and the number of dividing cells was decreased in Netrin-5 knockout mice. In addition, the formation of RMS was disorganized (Ikegaya et al., Front Neuroscience, 2020).
These results indicate that loss of function of Netrin-5 may reflect aging of the brain. In addition, we found that cerebral infarction caused strong upregulation of Netrin-5 in neuroblast and vascular endothelial cells. Therefore, it is expected that new methods such as the establishment of a neurotrophic factor release using the Netrin-5 promoter will be applied to the regeneration of cerebral infarction.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

Netrin-5ノックアウトマウスでニューロブラストの細胞分裂周期の延長と分裂細胞数の減少が見られたため、脳の老化を反映している可能性が考えられる。すなわちNetrin-5投与による脳老化の抑制効果が期待される。また、脳梗塞時にはニューロブラストおよび血管内皮細胞でNetrin-5の強い発現亢進が見られた。したがって、Netrin-5プロモーターを用いた神経栄養因子の放出方法の樹立など、今後視点を変えた新規手法により脳梗塞再生に向けての発展応用が期待される。