Identification of novel factors mediating the effects of environmental enrichment in the absence of voluntary exercise on psychiatric disorders

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19714
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Ago Yukio 広島大学, 医系科学研究科(歯), 教授 (50403027)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 環境強化 / 精神疾患 / 運動 / マウス / 樹状突起スパイン

Outline of Final Research Achievements

Mice lacking the gene encoding pituitary adenylate cyclase-activating polypeptide (PACAP) display some remarkable behavioral changes, including hyperactivity and abnormal jumping behavior in a novel environment and deficits in learning and memory. In humans, the dysregulation of PACAP and its specific receptor PAC1 has been associated with schizophrenia, depression, and post-traumatic stress disorder. In this study, we found that abnormal behaviors of PACAP-deficient mice were prevented by rearing in an enriched environment, but not by voluntary exercise using a running wheel. Our results also suggest that signals different from brain-derived neurotrophic factor are involved in the suppression of abnormal behaviors by environmental enrichment in the absence of wheel running. To elucidate this mechanism, we performed the differential gene expression analysis and identified several candidate molecules.

Free Research Field

中枢神経系薬理学

Academic Significance and Societal Importance of the Research Achievements

多くの精神疾患において遺伝的要因の関与が示されているが、その発症には個々の出生・生育環境、社会環境等の環境因子が関わっている。ヒトが日々健康的に生活をおくるうえで、身体活動・運動の重要性は広く認知されており、また末梢神経障害、スポーツ障害や外傷等からの機能回復において、運動療法が治療の一環として行われる場合もある。一方で発育早期や高齢時、また精神疾患や発達障害の場合においては、十分な、あるいは自発的な運動は困難である。本研究は、精神疾患モデルマウスを用いた環境要因の影響の解析から、運動によらない環境強化による脳機能保護という新たな可能性を示し、その分子基盤解明のための新しい方法論を構築した。