Metabolomic identification of molecular changes associated with stress resilience in the chronic mild stress rat model of depression

Chronic stressful events are key risk factors for major depressive disorder (MDD), yet some individuals exposed to stressful events do not develop MDD. This disparity suggests the significance of resilience to deleterious stress effects. However, the underlying molecular mechanisms of stress resilience are poorly understood. In the present study, the chronic mild stress (CMS) rat model of depression was used to reveal the individual differences in stress response. Employing a gas chromatography/mass spectrometry metabolomic approach, the molecular changes associated with stress resilience in rat cerebellum were characterized by comparing anhedonic, CMS resilient and control groups. The results showed that four cerebellar metabolites-proline, lysine, glutamine, and dihydroxyacetone phosphate-were identified as the key differential metabolites associated with stress resilience. These metabolites may play a potential role in rendering individuals less vulnerable to CMS exposure. These findings provide insight into the molecular mechanisms underlying stress resilience and shed light on novel therapeutic opportunities to augment stress resiliency.