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TOB is an effector of the hippocampus-mediated acute stress response
https://oist.repo.nii.ac.jp/records/2743
https://oist.repo.nii.ac.jp/records/27436c40a2ee-2aa7-4251-aee4-b72181d677a0
名前 / ファイル | ライセンス | アクション |
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Youssef-2022-TOB is an effector of the hippoca (4.7 MB)
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CC BY 4.0
Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/) |
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-08-08 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | TOB is an effector of the hippocampus-mediated acute stress response | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Youssef, Mohieldin M. M.
× Youssef, Mohieldin M. M.× Hamada, Hiro Taiyo× Lai, Esther Suk King× Kiyama, Yuji× El-Tabbal, Mohamed× Kiyonari, Hiroshi× Nakano, Kohei× Kuhn, Bernd× Yamamoto, Tadashi |
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書誌情報 |
en : Translational Psychiatry 巻 12, 号 1, p. 302, 発行日 2022-07-29 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior. | |||||
出版者 | ||||||
出版者 | Nature Portfolio | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2158-3188 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/35906220 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1038/s41398-022-02078-7 | |||||
権利 | ||||||
権利情報 | © 2022 The Author(s) | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.nature.com/articles/s41398-022-02078-7 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |