Exercise protects against chronic restraint stress-induced oxidative stress in the cortex and hippocampus.

Chronic stress induces high levels of reactive oxygen species, creating a neurotoxic environment. Because exercise protects against the neurodegenerative effects of oxidative stress, we investigated the protective effects of exercise against chronic restraint stress (CRS)-induced expression of the proapoptotic cortical B-cell associated X protein (Bax) and cyclooxegenase-2 (Cox-2) as well as microglial/macrophage proliferation and co-expression of Cox-2 in the cortex and hippocampus of mice. CRS induced a large, moderately significant increase in protein levels of Bax 1 h following stress. However, exercised mice had significantly lower cortical levels of Bax at both the 1 and 24 h time points. The level of Cox-2 protein was also significantly lower in the cortex of exercised mice. While no significant changes in microglia/macrophage proliferation were observed in either brain region, CRS induced significant increases of Cox-2 labeling on microglia/macrophages in both the hippocampus and cortex of stressed mice. In the cortex, stressed mice showed significantly greater numbers of Iba1/Cox-2 co-labeled cells than non-stressed mice; however, exercise alone did not induce any changes. In the hippocampus, CRS induced significantly greater numbers of Cox-2 labeled microglia/macrophages in stressed sedentary animals as compared to non-stressed controls. However, exercised mice were protected against these increases, as there was no significant difference in the numbers of Iba1/Cox-2 co-labeled cells between stressed and non-stressed exercised mice. Therefore, exercise protects against CRS-induced increases in levels of Bax in the cortex, and microglial/macrophage expression of Cox-2 in the hippocampus. Taken together, these data suggest that exercise may confer neuroprotection by acting to increase the resilience of the brain against CRS-induced oxidative stress. Published by Elsevier B.V.