Pathophysiological significance of astrocyte in developmental disorders with gene abnormalities

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21589
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: Nagata Koh-ichi 愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 部長 (50252143)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: アストロサイト / 発達障害 / モデルマウス

Outline of Final Research Achievements

Astrocytes are the most abundant cell type in mammalian brains. They play essential roles not only in physiological functions, but also in the neural network formation through regulating synaptogenesis and synapse elimination during the cortical development and maturation, suggesting that their functional deficits may cause neurodevelopmental disorders. Despite their potential importance, how astrocytes are involved in pathophysiology of neurodevelopmental disorders are poorly understood. In this study, we have developed a analytical battery for astrocytes. With this battery, we recapitulated haploinsufficiency conditions of RBFOX1 and NR1D1 genes in astrocytes. We then analyzed the knockdown effects of these genes on astrocytes per se and surrounding cortical neurons.

Free Research Field

小児発達障害

Academic Significance and Societal Importance of the Research Achievements

脳機能におけるアストロサイトの重要性が大きくクローズアップされ、その形態・機能異常が病態形成に関連する可能性も高い。しかしながら、これまで、アストロサイトの機能異常に焦点を当てた発達障害の分子病態メカニズム解析は殆どされていない。アストロサイトに着目してin vivo/in vitro解析バッテリーを構築し、発達障害の病態メカニズムを新規の観点から捉え直す点で、本企画の学術的意義は非常に大きい。