Abstract
Increasing evidence shows that stress contributes to the pathogenesis of major depressive disorder which is a severe neuropsychiatric disorder and influences over 10% of the world's population. Our previous studies revealed that rats reared in an enriched environment display less depression-related behavior compared to rats raised in an isolated environment, which implies that environmental enrichment produces an antidepressant-like behavioral phenotype. However, the molecular mechanisms are not fully understood. Protein phosphorylation rapidly changes signaling pathway function and alters the function of proteins associated with the stress-induced depressive disorder. Thus, in this study, a phosphoproteomic approach was used to uncover differential phosphoprotein regulation in rat nucleus accumbens between isolated (IC) and enriched environmental conditions (EC) under basal conditions, and in response to acute stress. We found 23 phosphoproteins were regulated in EC vs. IC rats under basal conditions; 10 phosphoproteins regulated by stress in IC rats; and 15 regulated by stress in EC rats. Among all significantly regulated phosphoproteins, 11 of them were represented in at least two conditions. The regulated phosphoproteins represent signaling pathway proteins (including ERK2), enzymes, transcriptional regulators, protein translation regulators, transporters, chaperones and cytoskeletal proteins. These findings provide a global view for further understanding the contribution of protein phosphorylation in depression pathogenesis and antidepressant action.
Highlights
Increasing evidence shows that stress contributes to the pathogenesis of major depression, which is a severe neuropsychiatric disorder that influences about 10% of the world population [1]
The phosphoproteins were analyzed by Progenesis SameSpots, and a total 55 differentially-phosphorylated protein spots in both fractions were subjected to MALDI TOF/TOF MS/ MS and/or Nano-LC MS-MS analysis
Altered phosphoproteins in nucleus accumbens (NAc) comparing environmental conditions (EC) vs. IC control rats
Summary
Increasing evidence shows that stress contributes to the pathogenesis of major depression, which is a severe neuropsychiatric disorder that influences about 10% of the world population [1]. Preclinical and clinical studies indicate that around 20% to 25% of people who experience major stressful events develop major depression, and most severe events rapidly lead to depression in women [2,3]. The depressed patient is impaired in reward and decision-making [4]. Molecular and cellular studies in rodents indicate that chronic stress leads to a depressive phenotype which is associated with changes in neurochemicals and several proteins in nucleus accumbens (NAc). The findings reveal NAc plays an important role in stress-induced depression [4]. The molecular mechanisms of stress-induced pathological changes contributing to depression remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
