Beneficial effects of running exercise on hippocampal microglia and neuroinflammation in chronic unpredictable stress-induced depression model rats

Running exercise has been shown to relieve symptoms of depression, but the mechanisms underlying the antidepressant effects are unclear. Microglia and concomitant dysregulated neuroinflammation play a pivotal role in the pathogenesis of depression. However, the effects of running exercise on hippocampal neuroinflammation and the number and activation of microglia in depression have not been studied. In this study, rats were subjected to chronic unpredictable stress (CUS) for 5 weeks followed by treadmill running for 6 weeks. The depressive-like symptoms of the rats were assessed with a sucrose preference test (SPT). Immunohistochemistry and stereology were performed to quantify the total number of ionized calcium-binding adapter molecule 1 (Iba1)+ microglia, and immunofluorescence was used to quantify the density of Iba1+/cluster of differentiation 68 (CD68)+ in subregions of the hippocampus. The levels of proinflammatory cytokines in the hippocampus were measured by qRT-PCR and ELISA. The results showed that running exercise reversed the decreased sucrose preference of rats with CUS-induced depression. In addition, CUS increased the number of hippocampal microglia and microglial activation in rats, but running exercise attenuated the CUS-induced increases in the number of microglia in the hippocampus and microglial activation in the dentate gyrus (DG) of the hippocampus. Furthermore, CUS significantly increased the hippocampal levels of inflammatory factors, and the increases in inflammatory factors in the hippocampus were suppressed by running exercise. These results suggest that the antidepressant effects of exercise may be mediated by reducing the number of microglia and inhibiting microglial activation and neuroinflammation in the hippocampus.