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The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Combined enriched environment and fluoxetine enhance myelin protein expression in the prefrontal cortex of a chronic
Jingyang Gu1,2, Cong Liu1,2, Yan Li3
1Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China.
Background:
The primary protein components of white matter include myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Alterations in their expression are significantly implicated in depression. This study investigated changes in MBP and CNP expression associated with depressive-like behaviors induced by chronic unpredictable stress (CUS) and evaluated therapeutic interventions using fluoxetine (FLU), an enriched environment (EE), or their combination.
Methods:
Male Sprague Dawley rats were randomly assigned to a control group and four CUS-exposed groups undergoing 6 weeks of stress. During the final 3 weeks of CUS, rats received daily fluoxetine (CUS + FLU group), were housed in EE (CUS + EE group), or received combined EE and fluoxetine (CUS + FLU + EE group). Depression-like behaviors were assessed through sucrose preference, forced swimming, and open field tests after CUS completion and at the end of weeks 4-6. Protein and mRNA expression levels of MBP and CNP in the prefrontal cortex were quantified via immunohistochemistry, western blot, and qRT-PCR.
Results:
Three weeks following CUS exposure, rats demonstrated significant depression-like behavioral phenotypes. By the fifth week, these behavioral deficits were ameliorated in the CUS + FLU + EE, whereas the CUS + FLU and CUS + EE groups exhibited comparable behavioral recovery by week 6. Parallel molecular analyses revealed diminished protein and mRNA expression levels of MBP and CNP in the prefrontal cortex of CUS-exposed animals, accompanied by a pronounced elevation in IL-1β expression. Therapeutic interventions with FLU, EE, or their combination significantly attenuated these CUS-induced molecular alterations.
Conclusions:
The antidepressant effects correlated with restored MBP, CNP, and IL-1β expression levels, suggesting that MBP/CNP deficiencies in depression may involve IL-1β elevation. In particular, combined enriched environment and fluoxetine accelerated behavioral recovery.
