Swimming exercise reverses CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins

Stress-induced failed resilience of brain plasticity can contribute to the onset and recurrence of depression. Chronic stress has been reported to open windows of epigenetic plasticity in hippocampus. However, how hippocampal plasticity underlies depression-like behaviors and how it adapts in response to stress has not been addressed. The present study aimed to investigate the signaling mechanisms of CUMS affecting hippocampal plasticity-related proteins expression and the regulation of swimming exercise in mice.Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 7 weeks. From the 4th week, CUMS mice were trained in a moderate swimming program for a total of 4 weeks. A videocomputerized tracking system was used to record behaviors of animals for a 5-min session. Real-time PCR and Western Blotting were used to examine gene expression in mouse hippocampus.Our results demonstrated that CUMS induced depression-like behaviors, which were reversed by swimming exercise. Moreover, the behavioral changes induced by CUMS and exercise were correlated with hippocampal plasticity-related proteins expression of growth-associated protein-43 (GAP-43) and synaptophysin (SYN). The molecular mechanisms regulating this plasticity may include SIRT1/mircoRNA, CREB/BDNF, and AKT/GSK-3β signaling pathways.We did not establish a correlation between depression-like behaviors induced by chronic stress and epigenetic changes of hippocampal plasticity, either a causal molecular signaling underling this plasticity.Our findings have identified swimming exercise effects on CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins, which provide a framework for developing new strategies to treat stress-induced depression.