Effects of exercise on disease progression and cognition in the marmoset EAE model
K.A. Phillips1,2, M.K. Hambright3, K. Hewes1, B.M. Schilder4, A. Jagessar5, B. 't Hart5, S.D. Tardif2
1Psychology, Trinity University, 2Southwest National Primate Research Center, San Antonio, TX, 3College of Coastal Georgia, Brunswick, GA, 4George Washington University, Washington, DC, United States, 5Biomedical Primate Research Centre, Rijswijk, The Netherlands
A growing body of evidence indicates physical activity is beneficial for brain health and function. Aerobic exercise promotes adult neurogenesis and neurotrophic factor expressions, has a neuroprotective effect against volumetric loss of the hippocampus, and may buffer cognitive impairment associated with aging and disease. We investigated the effects of regular, moderate exercise on disease onset, spatial memory and brain health in the experimental autoimmune encephalomyelitis (EAE) marmoset model of multiple sclerosis. Twelve adult male marmosets were randomly assigned to one of four experimental conditions:
a) EAE induced by myelin oligodendrocyte glycoprotein residues 34 - 56 (pMOG) and exercise (n = 4);
b) EAE induced by pMOG and no exercise (n = 4); placebo and exercise (n = 2); or placebo and no exercise (n = 2).
We assessed cognitive dysfunction using the radial arm maze (RAM) spatial memory task and tested for associations with brain health, which we assessed through the quantification of glial fibrillary acidic protein (GFAP) in serum and prefrontal cortex samples. Baseline measures included blood draws, training on RAM, and initial exercise protocol training. Over the course of 10 weeks, subjects were tested weekly on RAM. Assessment of clinical symptoms occurred daily. End of project measures included a blood draw and extraction of the brain. EAE marmosets that exercised showed a delayed onset of clinical symptoms (M = 53.5 ± 6.4 days versus M = 37.5 ± 9.1 days) and a reduction in errors in the spatial memory task (M = 4.75 errors versus M = 12.38 errors) compared to EAE marmosets that did not exercise. Serum GFAP concentrations were reduced and GFAP concentration in the prefrontal cortex was increased in EAE subjects who exercised. As the release of GFAP from brain tissue into the blood stream is an indicator of the loss of astrocytic structural integrity, the GFAP results indicate improved brain health via less degradation of astrocytes. Collectively, our results suggest that exercise has beneficial effects on brain health and function in the marmoset EAE model.
K.A. Phillips1,2, M.K. Hambright3, K. Hewes1, B.M. Schilder4, A. Jagessar5, B. 't Hart5, S.D. Tardif2
1Psychology, Trinity University, 2Southwest National Primate Research Center, San Antonio, TX, 3College of Coastal Georgia, Brunswick, GA, 4George Washington University, Washington, DC, United States, 5Biomedical Primate Research Centre, Rijswijk, The Netherlands
A growing body of evidence indicates physical activity is beneficial for brain health and function. Aerobic exercise promotes adult neurogenesis and neurotrophic factor expressions, has a neuroprotective effect against volumetric loss of the hippocampus, and may buffer cognitive impairment associated with aging and disease. We investigated the effects of regular, moderate exercise on disease onset, spatial memory and brain health in the experimental autoimmune encephalomyelitis (EAE) marmoset model of multiple sclerosis. Twelve adult male marmosets were randomly assigned to one of four experimental conditions:
a) EAE induced by myelin oligodendrocyte glycoprotein residues 34 - 56 (pMOG) and exercise (n = 4);
b) EAE induced by pMOG and no exercise (n = 4); placebo and exercise (n = 2); or placebo and no exercise (n = 2).
We assessed cognitive dysfunction using the radial arm maze (RAM) spatial memory task and tested for associations with brain health, which we assessed through the quantification of glial fibrillary acidic protein (GFAP) in serum and prefrontal cortex samples. Baseline measures included blood draws, training on RAM, and initial exercise protocol training. Over the course of 10 weeks, subjects were tested weekly on RAM. Assessment of clinical symptoms occurred daily. End of project measures included a blood draw and extraction of the brain. EAE marmosets that exercised showed a delayed onset of clinical symptoms (M = 53.5 ± 6.4 days versus M = 37.5 ± 9.1 days) and a reduction in errors in the spatial memory task (M = 4.75 errors versus M = 12.38 errors) compared to EAE marmosets that did not exercise. Serum GFAP concentrations were reduced and GFAP concentration in the prefrontal cortex was increased in EAE subjects who exercised. As the release of GFAP from brain tissue into the blood stream is an indicator of the loss of astrocytic structural integrity, the GFAP results indicate improved brain health via less degradation of astrocytes. Collectively, our results suggest that exercise has beneficial effects on brain health and function in the marmoset EAE model.