Effects of Voluntary Exercise on the Pathogenesis of Experimental Autoimmune Encephalomyelitis
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+CD45hi 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.