Research on neuronal dematuration disorder hypothesis of depression
| Project/Area Number |
19K06961
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 脳・神経 / うつ病 / 海馬 |
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| Outline of Research at the Start |
本研究ではマウスモデルを用いて、生理的刺激による神経脱成熟の障害が、うつ病の病態に関与する可能性を検討する。豊富環境飼育による脱成熟誘導を確定し、その障害を示すモデルを探索する。その際、既存のうつ病のモデルマウスを再評価するとともに、脂質生合成経路を障害した新規モデルのスクリーニングを行う。さらに、豊富環境における探索的行動を指標としたうつ様行動の新規評価系を確立し、AAVによる脂質生合成経路等の操作手法を活用して、脱成熟障害とうつ様行動の関係を明らかにする。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks2021
Author(s)
M. Asada-Utsugi, K. Uemura, M. Kubota, Y. Noda, Y. Tashiro, T. M. Uemura, H. Yamakado, M. Urushitani, R. Takahashi, S. Hattori, T. Miyakawa, N. Ageta-Ishihara, K. Kobayashi, M. Kinoshita, A. Kinoshita
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Journal Title
Molecular Brain
Volume: 14
Issue: 1
Pages: 23-23
DOI
Related Report
Peer Reviewed / Open Access
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