Effects of exercise on neuroprotection in experimental autoimmune encephalomyelitis
Pryor, William Milton
MetadataShow full item record
Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system that results in continued loss of cognitive, sensory, and motor function. In this study we aimed to evaluate the effects of voluntary exercise on the hallmarks of neuropathology and activation of pro-survival pathways in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. C57BL/6J mice were injected with an emulsion containing myelin oligodendrocyte glycoprotein (MOG) and then randomized to housing with a running wheel or a locked wheel. EAE mice exposed to exercise displayed less severe neurological disease score and later onset of disease when compared to sedentary EAE animals. Immune cell infiltration and demyelination in the ventral white matter tracts of the lumbar spinal cord was significantly reduced in the EAE exercise group compared to sedentary EAE animals. Axon immunolabeling in the ventral pyramidal and extrapyramidal motor tracts displayed a more random distribution of axons and apparent loss of smaller diameter axons with a greater loss of immunolabeling in the sedentary EAE animals. In lamina IX grey matter regions of the lumbar spinal cord, sedentary animals with EAE displayed a greater loss of α-motor neurons when compared to EAE animals exposed to exercise. Phosphorylation of TrkB receptors was significantly increased in the exercise group when compared to sedentary EAE animals and was distributed throughout the ventral horn and α-motor neurons. Expression of mitochondrial outer membrane pro-survival members Bcl-2, Bcl-XL, and Mcl-1 were all significantly higher in the EAE animals exposed to exercise. These data suggest that chronic voluntary exercise positively alters the autoimmune response and activates intrinsic pathways that lead neuroprotection.