Roles of astrocytic cell adhesion molecules in the regulatory mechanisms of the maintenance and disruption of neuronal network

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Kobe University
• Principal Investigator: MIYATA Muneaki 神戸大学, 医学研究科, 特命助教 (90582007)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞間接着分子 / アストロサイト / 神経細胞 / 三者間シナプス / 神経回路

Outline of Final Research Achievements

The molecular mechanisms for the astrocyte ramifications and functional polarization, as well as astrocyte-synapse interactions during tripartite synapse formation, have not fully been understood, because a coculture system in which cocultured astrocytes and neurons form tripartite synapses structurally and functionally similar to those in vivo had not been developed. We developed an in vitro coculture system in which astrocytes cocultured with neurons formed highly ramified structures with numerous fine processes. In this study, using this coculture system and gene-deficient mice, we identified adhesion molecules localized at the astrocyte-synapse interaction sites, and found that these molecules induce astrocyte functional polarization, play cooperative roles in tripartite glutamatergic and GABAergic synapse formation, and regulate neuronal network both in vitro and in vivo.

Free Research Field

細胞生物学、神経形態学

Academic Significance and Societal Importance of the Research Achievements

シナプスの構造、構成分子、形成機構および機能については国内外で精力的に研究され、全貌が解明されつつある。しかし、アストロサイト突起とシナプスの接着については、生体内に近い形態を示すアストロサイトの培養法が確立されていなかったため、ほとんど解明されていなかった。本研究によって興奮性および抑制性三者間シナプスの形成・維持と、これらのシナプスによって形成される神経回路の制御機構の一端が解明されれば、その成果の学術的意義は高い。また、本研究の成果は精神神経疾患の新しい診断法や治療法の開発にも繋がることが期待され、社会的意義も高い。