Effects of Voluntary Exercise on the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Background: Little is known about the effects of exercise using experimental autoimmune encephalomyelitis (EAE). Some evidence suggests that exercise during EAE may attenuate disease onset and severity. However, to our knowledge, no research exists on the effects of voluntary exercise in the relapsing-remitting model of EAE. We believe this to be important as the majority of persons diagnosed with MS demonstrate a relapsing-remitting clinical course. 

Objectives: We investigated the effects of voluntary exercise (i.e., wheel running) on disability scores and pathogenesis in mice during disease onset and course of a relapsing-remitting EAE model. 

Methods: 31 female SJL/J mice were subcutaneously injected with the encephalitogenic myelin antigen proteolipid protein (PLP)139-151 emulsified in Complete Freunds Adjuvant (CFA). Mice were then randomly assigned into either voluntary exercise (i.e., wheel running; n=15) or sedentary (n=16) groups. Mice were weighed and scored daily for EAE disability using a blinded rater. Disease onset was recorded as the first day of a score of greater than 0 per mouse. Mice were euthanized 29 days after induction. Brains and spinal cords were taken for histological analysis, phenotype of CNS infiltrating lymphocytes using flow cytometry, and PLP-specific responses from isolated CNS-ILs by ELISA.  

Results: The incidence of EAE did not differ between sedentary (14/16; 88%) and exercise (14/15; 93%) groups.  There was a day by condition interaction on percent change in body weight (F(1,28=1.920,p<0.05), but not EAE disability score (F(1,28)=1.179,p=0.25). There was no condition main effect (F(1,9)=0.016,p=.901), but there was a day main effect (F(1,28)=7.785,p<0.05) whereby EAE disability changed in a predictable pattern over the 29-day period. There was no significant difference in peak disability score between groups (p=0.95). There was a significant difference in the day of disease onset such that mice in the wheel running group demonstrated disability scores earlier compared to the sedentary group (p<0.05). There were no differences between groups in the percentage of infiltrating CD3⁺ T-cells, CD19⁺ B-cells or CD11b⁺CD45^hi macrophages or the percentage of Th1 cells isolated from the CNS.

Conclusions: Our findings provide evidence that voluntary exercise minimally impacts disability and disease course in mice with relapsing-remitting EAE. We believe a repeated study that is extended for a longer period of time post induction is necessary in order to elucidate the possible longer-lasting effects of exercise on EAE.