Molecular mechanisms of Excitatory and Inhibitory imbalance in Autism Spectrum Disorders

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07327
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokai University
• Principal Investigator: Hanno Yoko 東海大学, 医学部, 特定研究員 (50451860)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 自閉スペクトラム症 / 環境的要因 / E/Iバランス / 抑制性神経細胞 / 分化

Outline of Final Research Achievements

I found that a subtype of inhibitory neurons decreased in ASD model mice, and that increased activity of a molecular signal necessary for neuronal development and differentiation is important for this. When a drug that suppresses this molecular signal was administered to ASD mice, both the decreased number of these neurons and ASD symptoms were restored. However, suppressing molecular signals targeting these neurons recovered only social behavior of ASD symptoms. These data suggested that the increase in these molecular signals in ASD mice during development and the accompanying decrease in specific subtypes of neurons are important for the abnormalities in social behavior that is a core symptom of ASD.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、異なる二種類のASDの環境的要因によるモデルマウスにおいて、E/Iバランスの異常の原因となる発生時期特異的な大脳皮質の特定の抑制性神経細胞が減少する分子メカニズムの一端が明らかとなった。全く異なる環境リスク要因で共通であることから、ASD発症に共通する分子シグナルの変化である可能性が考えられる。また、ASDモデルマウスに対し発生や分化に重要な分子シグナルを脳発生期で制御することによって神経細胞の異常やASDの中核症状の改善が見られたことから、将来のASD治療に繋がる可能性を見出した。