2022 Fiscal Year Final Research Report
Elucidation of the molecular mechanisms responsible for social stress-induced dendritic atrophy and establishment of its control methods
| Project/Area Number |
20K07288
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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 48030:Pharmacology-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ストレス / 前頭前皮質 / 樹状突起 / シナプス / 三次元電顕 / 膨張顕微鏡法 / マウス / 中央代謝系 |
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| Outline of Final Research Achievements |
Excessive social and environmental stress leads to cognitive and emotional changes with a histological basis in morphological atrophy of prefrontal cortical neurons. However, the molecular and cellular mechanisms responsible for the atrophy of dendrites and synaptic structures are largely unknown. By visualizing prefrontal dendrites and synapses using super-resolution microscopy and 3D electron microscopy in chronic social defeat stress in mice, we found that mitochondria are involved in stress-induced structural atrophy of dendrites and synapses. Synaptosome-specific proteomic analysis revealed that the expression of molecules involved in the central metabolic system is altered after chronic stress, and that manipulation of the expression of molecules responsible for the central metabolic system in the prefrontal cortex can suppress stress-induced synaptic shrinkage and depressive-like behaviors.
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| Free Research Field |
神経科学、薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
ストレスによる脳機能変化において神経細胞の機能構造変容の重要性は示唆されてきたが、その分子機序には不明な点が多い。本研究は、微細構造観察と定量プロテオミクス解析、脳領域特異的な分子操作を駆使することにより、ストレスによる神経細胞の構造退縮やうつ様行動に、中央代謝系が関わることを見出した。今後は、ストレスによる中央代謝系の変化を担う分子機序を明らかにすることによって、神経伝達物質を標的とする既存の抗うつ薬とは異なる作用機序を有する新たな創薬標的候補の創出に繋がると考えられる。
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