2022 Fiscal Year Final Research Report
Constructive understanding of multi-layer processes underlying stress-induced cognitive and emotional changes and their implications for mental illnesses
| Project Area | Constructive understanding of multi-scale dynamism of neuropsychiatric disorders |
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| Project/Area Number |
18H05429
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
那波 宏之 和歌山県立医科大学, 薬学部, 教授 (50183083)
澤田 誠 名古屋大学, 環境医学研究所, 教授 (10187297)
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| Project Period (FY) |
2018-06-29 – 2023-03-31
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| Keywords | ストレス / 精神疾患 / 多階層オミクス / 神経回路 |
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| Outline of Final Research Achievements |
Stress increases the risk of mental illness, but the causal mechanisms linking the whole body-circuit-cell-molecule hierarchy that controls stress-induced cognitive and emotional changes are unknown. In this study, focusing on neuroinflammation and dopaminergic systems, we investigated the biological basis of stress susceptibility by identifying stress-induced molecular and neural circuit alterations in various brain regions and cell types, visualizing functional and morphological changes in neural circuits from the synaptic level to local and distributed circuits, and conducting molecular and opto/chemogenetic manipulations. As a result, we discovered in rodents the molecular mechanisms of stress-induced microglial response, the nature of leukocyte mobilization, the relationship between neural circuits such as dopaminergic systems and synaptic alterations, bioactive lipid production related to stress resilience, and the involvement of these changes in cognitive and emotional changes.
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| Free Research Field |
薬理学・神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を通じて、これまで不明な点が多かったストレス感受性とその生体反応を制御する生物学的基盤の一端が解明された。炎症性機序やドパミン系を中心に個体－回路－細胞－分子の階層間を繋ぐ因果律が解明されるとともに、従来予想できなかったストレスの分子経路の多様性や神経回路可塑性、ストレスレジリエンスを担う分子の実体、神経回路の実像等が同定され、脳科学・精神疾患研究において新たな概念を提示した。またストレス感受性制御における炎症反応の脳末梢連関の意義を示し、精神疾患におけるストレス病態のバイオマーカーや予防・治療法開発のための学術的な技術基盤を与えた。
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