Molecular basis of emotional behavior abnormalities induced by juvenile stress

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hiroshima University (2019); Hokkaido University (2016-2018)
• Principal Investigator: Yoshida Takayuki 広島大学, 医系科学研究科(医), 准教授 (60374229)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 幼若期ストレス / うつ様行動 / シナプス伝達 / 活動電位

Outline of Final Research Achievements

Using rodents, we investigated novel molecular, neural circuitry, and behavioral mechanisms related to postmaturity anxiety disorders or depressive like behavior caused by juvenile stress. The juvenile stress was associated with a decrease in instinctive elevated/novel environmental anxiety levels, an excess of fear memory extinction, a decrease in social anxiety levels, and an increase in depressive like behavior. In the amygdala of these juvenile stressed animals, an increased frequency of neuronal action potentials and low sensitivity to serotonin were observed. We also found that ketamine treatment improved depressive behavior, which was related to the restoration of the balance between excitatory and inhibitory synaptic inputs in the medial prefrontal cortex.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

不安障害や気分障害は脳内のセロトニンなどのモノアミン系神経伝達物質の低下が原因とする仮説が提唱されているが、本研究では、セロトニン作動性神経調節に加え、グルタミン酸作動性調節が情動機能調節に重要であり、その責任脳部位として扁桃体ならびに内側前頭前皮質における神経伝達修飾メカニズムが関与していることを電気生理学的、神経化学的ならびに行動学的に明らかにした。これは思春/青年期のストレス障害の発症機序ならびに神経精神基盤の成熟に与える影響について新規の分子・神経回路・行動メカニズムとして重要な知見であると考えられる。