Identification of 14-3-3 epsilon as a regulator of the neural apoptotic pathway for chronic-stress-induced depression
Yan Zhao,
Elizabeth J. Coulson,
Xingli Su,
Junfeng Zhang,
Baoyong Sha,
Hao Xu,
Yating Deng,
Yulong Chen,
Jian Cao,
Yunpeng Wang,
Shuang Wang
Affiliations
Yan Zhao
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Elizabeth J. Coulson
School of Biomedical Sciences, Faculty of Medicine and Queensland Brain Institute, the University of Queensland, Brisbane, QLD 4072, Australia
Xingli Su
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Junfeng Zhang
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Baoyong Sha
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Hao Xu
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Yating Deng
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Yulong Chen
Institute of Basic and Translational Medicine, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Jian Cao
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China
Yunpeng Wang
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Corresponding author
Shuang Wang
Institute of Basic Medicine Science & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China; Corresponding author
Summary: Major 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.
