Research on neuronal dematuration disorder hypothesis of depression

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Nippon Medical School
• Principal Investigator: Kobayashi Katsunori 日本医科大学, 医学部, 准教授 (10322041)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳・神経 / うつ病 / 海馬

Outline of Final Research Achievements

I have previously shown that antidepressant treatment induces dematuration, a change in neuronal phenotypes to an immature-like state, in the mouse hippocampus. In the present study, I have examined a possibility that impairment of physiological dematuration underlies the pathophysiology of depression. Chronic stress caused a sustained decrease in cage activity of mice housed in isolation. Antidepressant treatment combined with exercise induced dematuration in the stressed mice, but not in control mice, and restored the cage activity. Environmental enrichment induced dematuration-like changes in neuronal functions. Chronic stress had minor effects on behavior of mice housed in enriched environment. These results suggest that the induction of dematuration depends on environmental conditions, and that mice are more susceptible to stress-induced behavioral impairment when housed in environmental conditions that do not facilitate the induction of dematuration.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果はうつ病の病態解明と克服に貢献すると考えられる。本研究で観察した神経機能変化のメカニズムや、変化を生じさせる生体内外要因の理解がさらに進めば、うつ病の予防方法や治療方法の改善に結び付く知見が得られると期待される。特に、ストレスを受けた際に、それを弾き返してうつ病にならないようにする力、つまりレジリエンスを高める方法の開発や、生活習慣の提案に結び付くと考えられる。