interneurons and extracellular matrix in the central nervous system of aged mouse

Research Project

Project/Area Number	19K19422
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research Institution	Kawasaki University of Medical Welfare
Principal Investigator	Ueno Hiroshi 川崎医療福祉大学, 医療技術学部, 准教授 (60725068)
Project Period (FY)	2019-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords	高齢化 / マウス / 認知機能 / 行動解析 / 抑制性介在ニューロン / 細胞外マトリックス / 神経細胞周囲網 / 神経可塑性
Outline of Research at the Start	本研究では，これまでの研究成果を応用させ，認知機能の低下とその生物学的マーカーの探索を行う。そこで，高齢マウスの認知機能低下のレベルと組織学的所見，血液学的所見を検討する。これにより，認知機能低下を細胞外マトリックス分子の変化の点から理解し，認知機能経過の予測を行える検査の確立，治療薬の探索に繋げる。
Outline of Final Research Achievements	The details of the histological changes in inhibitory interneurons and extracellular matrix in the brains of mice with and without cognitive decline due to aging remain unclear. In particular, the details of histological changes due to aging of the perineuronal network, which is a special ECM structure that is thought to be selectively expressed around PV-positive neurons, remain unclear. A 12-month-old brain of an aging-accelerated model mouse (SAM mouse) was used. Behavioral abnormalities were observed in SAMP8 and P10 mice, and at the same time, abnormalities were observed in the expression of inhibitory interneurons and extracellular matrix. Changes in inhibitory interneurons and changes in ECM in the hippocampus seen in this study may be related.
Academic Significance and Societal Importance of the Research Achievements	本研究は高齢化によるマウスの行動異常と海馬の細胞外マトリックス分子と抑制性介在ニューロンの変化の関係性の一端を明らかにしたものであり，高齢化の認知機能低下の原因解明とその治療方法と予防方法の確立に寄与している。老齢マウスの脳の組織学的な変化を報告した研究はまだ少なく，今回の研究成果が認知機能低下を早期に発見するマーカーの礎になる可能性が高い。