Title (s): Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that affects sensory, motor, and cognitive function during development. About three million people in the world have reported MS, with a ratio of 3 to 2 between women and men. Also, nearly 45-70% of patients suffer from cognitive disorders. The protective effect of regular aerobic training on cognitive function has been revealed. In this study, we focused on the effects of regular aerobic swimming exercise, encephalomyelitis induced mild cognitive impairment and both of them together on the microRNA-1-3p expression and their relation to the brain-derived neurotrophic factor (BDNF) and synaptosomal protein (snap25).

Materials and Methods: 21 C57BL/6 mice were used randomly in three groups: control (7 samples), experimental autoimmune encephalomyelitis (EAE) without exercise (7 samples), and with 4 weeks of aerobic swimming exercise (7 samples). MicroRNA expression analysis by RT-PCR, BDNF and snap25 protein levels were measured by western blotting method. Also, Clinical scores and animal weights were recorded daily.

Findings: EAE induction up-regulated microRNA-1-3p, increased snap25 protein and decreased BDNF compared to the control group. Furthermore, female mice under exercise conditions showed significant down-regulation of the miR-1-3p (Pvalue: 0.0014, F: 23.88, R2: 0.89), decreased snap25 (Pvalue: 0.0003, F: 42.92, R2: 0.93) and increased BDNF (Pvalue: 0.0003, F: 44.05, R2: 0.94). In addition, miR-1-3p was inversely related with cognitive function and BDNF protein.

Conclusion: Our data demonstrated that regular swimming exercise for four weeks could reverse the up-regulation of brain tissue miR-1-3p, snap25 which has a probable role in the MS-induced mild cognitive impairment. It also seems that the increase of BDNF after exercise is related to mir-1-3p and snap25 reductions and improvement of cognitive performance.