Citation

Zhao Y, Coulson EJ, Su X, Zhang J, Sha B, Xu H, Deng Y, Chen Y, Cao J, Wang Y, Wang S. iScience 2021; 24(2).

Copyright

(Copyright © 2021, Cell Press)

DOI

10.1016/j.isci.2021.102043

PMID

unavailable

Abstract

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. © 2021 The Author(s); Neuroscience; Cell Biology; Proteomics © 2021 The Author(s)

Language: en

Keywords

Neuroscience; Proteomics; Cell Biology