Hippocampal proteomic changes of susceptibility and resilience to depression or anxiety in a rat model of chronic mild stress

Abstract

Chronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders. However, the stress-induced molecular mechanisms underlying the common and distinct pathophysiology of these disorders remains largely unclear. We utilized a chronic mild stress (CMS) rat model to differentiate and subgroup depression-susceptible, anxiety-susceptible, and insusceptible rats. The hippocampus was analyzed for differential proteomes by combining mass spectrometry and the isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique. Out of 2593 quantified proteins, 367 were aberrantly expressed. These hippocampal protein candidates might be associated with susceptibility to stress-induced depression or anxiety and stress resilience. They provide the potential protein systems involved in various metabolic pathways as novel investigative protein targets. Further, independent immunoblot analysis identified changes in Por, Idh2 and Esd; Glo1, G6pdx, Aldh2, and Dld; Dlat, Ogdhl, Anxal, Tpp2, and Sdha that were specifically associated to depression-susceptible, anxiety-susceptible, or insusceptible groups respectively, suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus. Collectively, the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model. This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety, and stress resiliency.

Chronic mild stress-induced protein dysregulations correlated with susceptibility and resiliency to depression or anxiety revealed by quantitative proteomics of the rat prefrontal cortex

“…The animals were habituated to sucrose consumption and the CMS procedure was carried out, as described previously 22 . Based on baseline sucrose intake from the three tests, the rats were divided randomly among the stressed or control units.…”

“…As previously described 22 , we conducted a sucrose preference test (SPT) to measure the rat depression-like behavior (anhedonia). The behavioral-based formula was used to assess sucrose preference: sucrose preference = (sucrose intake/total fluid intake) × 100%.…”

“…The behavioral-based formula was used to assess sucrose preference: sucrose preference = (sucrose intake/total fluid intake) × 100%. Afterward, a forced swimming test (FST) was conducted to gauge despair-like behavior, as formerly illustrated 22 . The behaviors of the rats were determined in a water-filled Plexiglas cylinder and recorded using a video monitoring system.…”

“…In our previous research, hippocampal quantitative proteome profiling was used to explore distinct and common proteins related to CMS-induced depression- and anxiety-like behaviors 22 . Based on the behavioral testing data, the depression-susceptible, anxiety-susceptible, and insusceptible groups were obtained to be used as the three different CMS responses.…”

“…Based on the behavioral testing data, the depression-susceptible, anxiety-susceptible, and insusceptible groups were obtained to be used as the three different CMS responses. In the present study, the prefrontal cortical tissues from this sample of CMS model rats 22 were utilized to further explore stress-induced depression and anxiety disorders. The proteomes of the prefrontal cortex from the depression-susceptible, anxiety-susceptible, insusceptible, and control groups were comparatively profiled, providing the molecular basis correlated to adaptive and maladaptive phenotypes of depression or anxiety.…”