title: Voluntary wheel running differentially affects disease outcomes in male and female mice with experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system. The primary symptoms of MS include the loss of sensory and motor function. Exercise has been shown to modulate disease parameters in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by reducing immune cell infiltration and oxidative stress. However, these initial studies were carried out exclusively in female mice. The present study compared the effects of daily voluntary wheel running on several disease parameters in male and female mice with EAE. Male and female mice were given access to a running wheel for 1h a day for 30 consecutive days. Daily wheel running significantly improved clinical scores in males with EAE but had little effect on clinical signs in females with the disease. Direct comparison of inflammation, axonal injury, and oxidative stress in male and female mice with EAE revealed significant differences in the amount of T-cell infiltration, microglia reactivity, demyelination and axon integrity. Male mice with EAE given daily access to running wheels also had significantly less ongoing oxidative stress compared to all other groups. Taken together, our results indicate that the inflammatory response generated in EAE is distinct between the sexes and its modulation by daily exercise can have sex-specific effects on disease-related outcomes.
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Mifflin
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Frieser
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Benson
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Psychiatry (NRU), University of Alberta, Edmonton, AB T6G 2G3, Canada.
authors.forename: Glen
authors.initials: G
authors.lastname: Baker
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Psychiatry (NRU), University of Alberta, Edmonton, AB T6G 2G3, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada; Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada. Electronic address: bradley.kerr@ualberta.ca.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Kerr
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000209:etiology / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D019803:Glutathione Disulfide / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D012420:Running / Q000502:physiology*; D012727:Sex Characteristics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D015704:CD4 Antigens; D002135:Calcium-Binding Proteins; D005620:Freund's Adjuvant; D019803:Glutathione Disulfide; D008840:Microfilament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009842:Oligopeptides; D010446:Peptide Fragments; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C491049:Aif1 protein, mouse; C535223:SM1 peptide; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: EAE; Exercise; GSH/GSSG; Multiple sclerosis; Oxidative stress; Running; Sex differences; Sod