Metabolic and Skeletal Muscle Dysfunctions Correlate with Fatigue-Like Behavior in an Animal Model of Multiple Sclerosis

The nature of cognitive and physical exhaustion suggests that MS fatigue can be a metabolic disease that impacts energy demanding processes such as neuronal activity and skeletal muscle contraction. In this study, we investigated how autoimmune-mediated inflammation causes skeletal muscle atrophy and metabolic dysfunctions, which may contribute to MS fatigue.

Using a relapsing-remitting model experimental autoimmune encephalomyelitis (EAE), we found that disease manifestations substantially altered the metabolic activities of the mice over time. EAE decreased muscle mass and force input in both fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles but only increased the rate of fatigue in EDL muscle. Gene expression analysis of EDL muscle shows that genes related to cellular respiration and mitochondrial functions were significantly down regulated during when EAE manifestations were the most severe, but this genotype was reversed during disease remission.