Dimensional approaches to psychiatric disorders associated with circuit abnormalities induced by genetic and environmental insults combined with inflammation in the brain

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03547
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kyoto University
• Principal Investigator: Sakurai Takeshi 京都大学, 医学研究科, 客員研究員 (90615717)
• Co-Investigator(Kenkyū-buntansha): 大槻 元 京都大学, 医学研究科, 特定教授 (60723278)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 社会性ストレス / 思春期 / マウスモデル / 脳内炎症

Outline of Final Research Achievements

There may be a wide variety of changes in reactivity and plasticity of neurons as well as reactivity of immune cells in many brain regions of mouse models that have genetic modification of synaptic molecules or maternal immune challenges during embryonic development. When social stress is applied to those brain regions during adolescence, circuitry specific effects in neuronal activities as well as stress responses in the entire brain may be induced, leading to behavioral changes in the domains relevant to psychiatric disorders such as schizophrenia. These results suggest the importance of developing strategy to increase mental resilience to social stress during adolescence to overcome vulnerability in the brain introduced by genetic and environmental factors.

Free Research Field

精神疾患の神経科学

Academic Significance and Societal Importance of the Research Achievements

精神疾患の発症リスクの高い人達には、発症以前から遺伝・環境要因による脳の脆弱性の存在が想定されているが、その脆弱性は神経生物学的に多様な事象が関わっており、さらにそこに思春期の社会性ストレスなどによって負荷がかかる事により成人での行動や認知機能異常につながると考えられる事が明らかとなった。今後、その原因毎の脳内の脆弱性の詳細な解析が必要なことに加え、現在問題となっているパンデミックによる社会的状況によってその増大が懸念されている思春期の社会性ストレスに対しては、科学的エビデンスに基づいた有効でかつ多様なメンタルヘルスサポートの必要性が示唆された。