Exercise reverses chronic stress-induced Bax oligomer formation in the cerebral cortex.

Chronic stress may lead to neuronal atrophy and functional impairments within the CNS, and increasing evidence indicates that exercise can protect the brain from these changes. Bax is a key protein of the B-cell lymphoma (Bcl) family that complexes within the mitochondrial membrane and forms pores to initiate cellular apoptosis. Herein, we measured cortical Bax levels following chronic and acute stress via immunoblotting. We reveal that chronic, but not acute, stress increases cortical levels of Bax oligomer 270, a complex revealed in previous studies to be associated with apoptosis. Several recent studies have revealed that physical exercise can protect rodents from neurochemical and/or behavioral changes occurring with stress. Previous studies have also revealed that voluntary exercise enhances the expression and activation of cellular proteins associated with enhanced neuronal survival. Herein, we reveal that 3 weeks of daily restraint led to increased oligomerization of Bax within the cerebral cortex, and that chronic corticosterone administration had a similar effect. Voluntary wheel running, concurrent with chronic restraint, prevented an increase in Bax oligomer 270. Analysis of subcellular fractions also revealed that the combination of exercise with chronic stress reduced the percent of total Bax localized to the mitochondria. Ours is the first study to investigate dynamic molecule complexes associated with the initiation of apoptosis with stress, and the influence of exercise upon the levels of these complexes, suggesting that exercise is an effective preventative measure that can promote neuronal survival and protect the brain against the damaging effects of chronic stress.