Structual and functional interaction between astrocyte and neuronal synapse

• Project/Area Number: 18K06513
• 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 (2020); Foundation for Biomedical Research and Innovation at Kobe (2018-2019)
• Principal Investigator: Miyata Muneaki 神戸大学, 医学研究科, 特命助教 (90582007)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 細胞間接着分子 / アストロサイト / 神経細胞 / シナプス / 三者間シナプス / 細胞接着分子 / 共培養 / Necl

Outline of Final Research Achievements

The molecular mechanisms for the astrocyte ramifications and functional polarization and the astrocyte-synapse interaction during tripartite synapse formation have not fully been understood, because the coculture system in which cocultured astrocytes and neurons form tripartite synapses structurally and functionally similar to those in vivo has not been developed. We developed the in vitro coculture system in which astrocytes cocultured with neurons formed high ramifications 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 and play cooperative roles in tripartite glutamatergic synapse formation in vitro and in vivo.

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が、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。本研究によってアストロサイト突起とシナプスの間の接着の形成・維持機構の一端が解明され、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。