Studying the mechanisms of spreading depression in the brain with fluorescent indicators located in intercellular spaces

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20659
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: MITA Marie 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (20964878)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 蛍光タンパク質 / ライブイメージング / 蛍光タンパク質センサー / プローブ / 脳 / 神経

Outline of Final Research Achievements

In stroke and/or traumatic brain injury, transient loss of neuronal excitability spreads from the damaged area to a wide range of the brain. This phenomenon, called as spreading depression, is thought to be mediated by some molecules that diffuse throughout the extracellular space. Fluorescent protein-based indicators have been widely used to observe many intracellular molecular dynamics of interest, but the applications for extracellular space were not very common. In this study, we observed the spatiotemporal dynamics of molecules in the extracellular space by using the fluorescent protein-based indicators immobilized in the extracellular space. This extracellular space imaging technique will be useful for the identification of molecules that cause spreading depression and to the elucidation of pathological mechanisms of many neurodegenerative diseases that relate to spreading depression.

Free Research Field

分子細胞生理学

Academic Significance and Societal Importance of the Research Achievements

従来のライブイメージング技術は、主に細胞内の分子動態を詳細に可視化し、細胞機能の解明に貢献してきたが、細胞間隙における細胞間相互作用を解明するための、細胞外の分子動態に適用されている例は少ない。脳卒中や脳損傷に起因する拡延性抑制は脳スライス標本で再現できるため、細胞レベルでの病態と細胞間隙における分子動態をイメージングから理解する格好の研究モデルとなる。拡延性抑制の伝播メカニズム解明は、脳機能障害の抑制薬の開発や、回復を早める治療法の確立などにつながることが期待できる。