Functional analysis of the mechanism of hyperactivity disorder caused by dopaminergic abnormality and psychological stress

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Umemura Mariko 東京薬科大学, 生命科学部, 講師 (30521489)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: モノアミン / 脳 / マウス / 行動異常

Outline of Final Research Achievements

In recent years, developmental disorders characterized by hyperactivity have increased, and one of the causes of hyperactivity is thought of the dopamine nervous system abnormality. We developed that the mouse deficient in the transcription factor ATF5, which regulates neuronal differentiation. ATF5 deficient mice exhibit abnormal behavior such as hyperactivity and incleased anxiety-like behavior. ATF5 deficient mice had decreased the dopamine levels in the amygdala, but not serotonin levels. In ATF5-deficient mice, there was no significant difference in amygdala structure, but excitatory neurons in the amygdala were decreased, and the number of dopamine receptors positive neurons was decreased. Taken together, it was expected that the ATF5 deficient mouse would have an abnormal dopamine signal in the brain, which may lead to hyperactivity.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

多動を特徴とした発達障害の脳内の原因の解明や、根本的な治療法や治療薬の開発はあまり進んでいない。本研究では、多動などの行動異常の原因解明のための新しい知見を得ることを目標として研究を進めた。ストレス応答性転写因子のATF5は、神経細胞の分化や増殖に関与する。このATF5欠損マウスは、多動や不安様行動の亢進がみられ、脳の扁桃体のドーパミン量が減少していた。また、ドーパミン受容体の発現に異常があることがわかった。このことから、ATF5欠損マウスでは、ドーパミンシグナル系の異常があることがわかった。この研究で得られた知見は、多動性障害の原因の解明に貢献すると期待される。