Exploration of novel excitatory/inhibitory balance control mechanisms in neural circuits for the treatment of neuropsychiatric disorders.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07065
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kagawa University
• Principal Investigator: Yamamoto Tohru 香川大学, 医学部, 教授 (10251480)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: E/Iバランス / MDGA1 / MDGA2 / 自閉スペクトラム症 / 統合失調症

Outline of Final Research Achievements

Focusing on abnormalities in the balance between excitatory and inhibitory inputs that underlie the molecular pathology of neuropsychiatric disorders, we analysed the behavioural tendencies of mice lacking the MDGA2 or MDGA1 genes, in which excitatory or inhibitory synapse formation is excessive, respectively, as a model system and also explored drugs that could improve behavioural abnormalities resembling neuropsychiatric disorders. As a result, it was revealed that the two mouse models have contrasting behavioural characteristics, especially in the social context, and drugs that can ameliorate these behavioural abnormalities were successfully identified.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

各種精神神経疾患に通底する分子病態である興奮性/抑制性入力バランス偏移がどのような認知行動異常をもたらしうるかを明らかにした。さらに、当該マウスモデルを用いてこうした異常を速やかに改善し得る薬物を探索し、候補となり得る薬物を得た。これにより、高次脳機能統御における興奮性/抑制性入力バランス制御の重要性をあらためて示すとともに、当該マウスモデルに類似した分子病態により引き起こされている精神神経疾患について、その治療方策の検討に資する知見を提供した。