{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:28:18Z","timestamp":1786429698367,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Multiple sclerosis associated fatigue (MS fatigue) is one of the most common and troubling symptoms experienced by people with MS, but the cause of MS fatigue remains unknown. 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 of 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 production in both fast extensor digitorum longus (EDL) and slow soleus muscles but only increased the rate of fatigue in the EDL muscle. Gene expression analysis of the EDL muscle shows that genes related to cellular respiration and mitochondrial functions were significantly downregulated when EAE manifestations were the most severe, but the phenotype was reversed during disease remission. In addition, EAE-induced mice showed fatigue behavior during a maximal treadmill test. Surprisingly, this fatigue behavior was also observed with mice immunized with a CNS non-specific antigen, suggesting there are contributions from central nervous system-independent immune activation. To our knowledge, this is the first report to characterize skeletal muscle properties and fatigue behavior in mice following EAE induction.<\/jats:p>","DOI":"10.3389\/fphys.2026.1892106","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:39:54Z","timestamp":1786426794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic and skeletal muscle dysfunctions correlate with fatigue behavior in an animal model of multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Kody M.","family":"Moore","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine","place":["Morgantown, WV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Whetsell","sequence":"additional","affiliation":[{"name":"Division of Exercise Physiology, 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