Influence of altered synapse pruning in the developing cerebellum on mouse behaviors relevant to autism spectrum disorder and schizophrenia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H04785
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Teikyo University (2023); The University of Tokyo (2021-2022)
• Principal Investigator: Kano Masanobu 帝京大学, 先端総合研究機構, 教授 (40185963)
• Project Period (FY): 2021-04-05 – 2024-03-31
• Keywords: シナプス刈り込み / 発達期 / 小脳 / マウス / 自閉スペクトラム症 / 統合失調症

Outline of Final Research Achievements

Cerebellar abnormalities are thought to contribute to the onset of autism spectrum disorder (ASD) and schizophrenia (SZ), but the relationship between synapse pruning in the developing cerebellum and these neuropsychiatric disorders remains unclear. In this study, we addressed this issue using mice with cerebellar Purkinje cell-specific deletion of a gene associated with ASD or SZ. Mice lacking a gene for a cell adhesion molecule associated with ASD exhibited enhanced synapse pruning and some ASD-like behavioral abnormalities. However, we could not establish a causal link between the two. On the other hand, mice with Purkinje cell-specific deletion of an SZ risk gene showed impaired synapse pruning and reduced behavioral flexibility. While our findings provide insights into the role of cerebellar synapse pruning in these neuropsychiatric disorders, further research is needed to draw definitive conclusions.

Free Research Field

神経科学一般、神経生理学

Academic Significance and Societal Importance of the Research Achievements

自閉スペクトラム症(ASD)や統合失調症(SZ)は、頻度が高く、患者の社会生活に影響する重要な精神神経疾患である。近年、これらの発症に小脳の異常が関わると広く考えられるようになった。一方、ASDやSZでは、発達期の大脳皮質のシナプス刈り込みに異常があることが知られているが、発達期の小脳におけるシナプス刈り込みの異常が関わるかは明らかでなかった。マウスを用いた本研究において、ASDやSZの関連遺伝子の小脳プルキンエ細胞特異的欠損がシナプス刈り込みの異常を起こすとともに、これらの精神疾患類似の行動異常を生じる可能性を示した。ASDやSZの病態生理の理解の進展に貢献する研究成果と考えられる。