文章基本信息

标题：Identification of 14-3-3 epsilon as a regulator of the neural apoptotic pathway for chronic-stress-induced depression
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作者：Yan Zhao ; Elizabeth J. Coulson ; Xingli Su 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-29
DOI：10.1016/j.isci.2021.102043
语种：English
出版社：Elsevier
摘要：SummaryMajor depression is a prevalent and long-lasting psychiatric illness with severe functional impairment and high suicide rate. We have previously shown that the ventrolateral orbital cortex (VLO) plays a key role in the stress responses in mice, but the underlying mechanisms remains unclear. Here, we used proteomic method to identify differentially expressed proteins in VLO of chronic unpredictable mild stress (CUMS) mice. Of 4,953 quantified proteins, 45 proteins were differentially expressed following CUMS. The integrated pathway analyses identified 14-3-3ε and TrkB signaling as differentially downregulated in association with stress-induced depressive-like behaviors. 14-3-3ε overexpression in VLO relieved the depressive-like behaviors by rescue of Bad-mediated apoptosis. Moreover, treatment with the 14-3-3ε stabilizer FC-A precluded neuronal apoptotic signaling in VLO of depressed mice. Because 14-3-3ε provides significant protection against chronic stress, boosting 14-3-3ε expression, pharmacological stabilization of 14-3-3s (e.g. with FC-A) is identified as an exciting therapeutic target for major depression.Graphical abstractDisplay OmittedHighlights•Novel screening of chronic mild stress-induced depression phenotypes in mice•Proteomics identify 14-3-3ε as a key modulator of depressive behaviors in VLO•14-3-3ε partially reversed depressive behaviors through neural apoptotic pathway•14-3-3ε stabilizer FC-A ameliorates depression phenotypes after chronic mild stressNeuroscience; Cell Biology; Proteomics