Chronic unpredictable stress-induced in Feeding Behavior and Emotional Phenotypes via Glp1R and MC4R Downregulation in the Nucleus Accumbens

초록

Stressful events are well-established risk factors for psychological disorders, particularly depression. Nevertheless, a substantial subset of individuals demonstrate resilience, maintaining stable psychological functioning despite repeated exposure to adversive stressors. While stress-induced symptoms such as anhedonia, dysregulated feeding behaviors, and behavioral despair are frequently observed, the precise synaptic and molecular mechanisms underlying these diverse phenotypes remain largely unknown. In this study, we examined the effects of chronic unpredictable stress (CUS) on behavior and gene expression in an inbred mouse model. Mice exposed to CUS exhibited significant behavioral alterations , including reduced sucrose preference (anhedonia), abnormal feeding patterns, and increased behavioral despair. Transcriptomic analysis using RNA sequencing revealed stress-specific gene expression changes in the nucleus accumbens (NAc), a key brain region involved in motivation and emotional regulation. Notably, we observed significant downregulation of glucagon-like peptide-1 receptor (Glp1R) and melanocortin 4 receptor (MC4R) genes in the NAc of stressed mice. Both genes play essential roles in appetite regulation, energy balance, and mood modulation. These findings suggest that stress-induced suppression of Glp1R and MC4R signaling within the NAc may contribute to disrupted feeding behavior and emotional dysregulation. Our study highlights a potential molecular pathway linking chronic stress to neurobehavioral outcomes and identifies promising targets for intervention in stress-related disorders.