Possible target-related proteins of stress-resistant rats suggested by label-free proteomic analysis

Abstract

Stress plays a crucial role in the development of major depressive disorder, but the molecular mechanism underlying the susceptibility vs. resilience to stress remains unclear. To better understand these mechanisms, we used chronic unpredictable mild stress to develop a depressive rat model. We categorized them into stress resistant rats and stress sensitive rats by their performance in behavioral tests, including forced swim test and sucrose preference test. Brain regions were dissected, and prefrontal cortex (PFC) proteins extracted from stress resistant and stress sensitive rats were analyzed using label-free liquid chromatography-tandem mass spectrometry. Three hundred and four proteins were up-regulated and 323 proteins were down-regulated among the 1482 different proteins from stress resistant rats compared with that of the stress sensitive rats. Western blotting, immunohistochemical staining and electron microscopy were used to validate the results of the proteomic analysis. Some proteins differentially expressed in stress resistant and sensitive rats were found to be associated with several neurobiological processes, particularly with neurotransmission regulation. The results provide possible novel insights into the molecular mechanisms for stress resilience.