Effect of voluntary wheel running on neuroactive steroid levels in murine experimental autoimmune encephalomyelitis

Increasing evidence from both clinical and animal research has implicated changes in neuroactive steroids (rapid acting steroids that act as allosteric modulators at NMDA and/or GABA-A receptors) in multiple sclerosis. These changes have been linked to clinical differences in disease severity, prevention of disease development, as well as the disease state (relapsing vs progressive) in patients with multiple sclerosis. Previous research has also linked changes in neuroactive steroid levels to the beneficial effects of exercise in certain disorders such as traumatic brain injury and post-traumatic stress disorder. The present study therefore examined whether voluntary wheel running could modulate any of the reported changes in neuroactive steroids associated with the EAE model of multiple sclerosis. Female mice with EAE who ran were found to have significantly increased levels of brain pregnenolone compared to male EAE mice who ran. In contrast, male mice with EAE were found to have significantly higher levels of brain allopregnanolone compared to female mice with EAE regardless of exercise. Overall, these results indicate that exercise has moderate beneficial effects on brain neuroactive steroid levels in EAE. These changes may be related to other beneficial responses to exercise, such as improvements in disease severity, in EAE and/or multiple sclerosis.