Swimming Exercise Ameliorates Symptoms of MOG-Induced Experimental Autoimmune Encephalomyelitis by Inhibiting Inflammation and Demyelination in Rats

Abstract

Purpose: Multiple sclerosis is an autoimmune disease that affects the central nerve system, resulting in cumulative loss of motor function. Multiple sclerosis is induced through multiple mechanisms and is caused by inflammation and demyelination. This study aims to evaluate the neuroprotective effect of swimming exercise in experimental autoimmune encephalomyelitis (EAE) rats, an animal model of multiple sclerosis.

Methods: EAE was induced by an intradermal injection of 50-μg purified myelin oligodendrocyte glycoprotein 33-55 (MOG33-55) dissolved in 200-μL saline at the base of the tail. The rats in the swimming exercise group were made to swim for 30 minutes once pert a day for 26 consecutive days, starting 5 days after induction of EAE. To compare the effect of swimming exercise with interferon-β, a drug for multiple sclerosis, interferon-β was injected intraperitoneally into rats of the EAE-induced and interferon-β-treated group during the exercise period.

Results: Injection of MOG33-55 caused weight loss, decreased clinical disability score, and increased level of pro-inflammatory cytokines and inflammatory mediators in the lumbar spinal cord. Loss of motor function and weakness increased demyelination score. Swimming exercise suppressed demyelination and expression of pro-inflammatory cytokines and inflammatory mediators. These changes promoted recovery of EAE symptoms such as body weight loss, motor dysfunction, and weakness. Swimming exercise caused the same level of improvement as interferon-β treatment.

Conclusion: The results of this experiment suggest the possibility of swimming exercise in urological diseases that are difficult to treat. Swimming exercises can be considered for relief of symptom in incurable multiple sclerosis.

Keywords: Demyelination; Experimental autoimmune encephalomyelitis; Inflammation; Multiple sclerosis; Swimming exercise.

Fig. 1.

Experimental schedule. MOG, myelin oligodendrocyte glycoprotein; IFN, interferon.

Fig. 2.

Body weight and clinical disability score. (A) Body weight during the experiment. (B) Clinical disability score during the experiment. ●, control group; □, experimental autoimmune encephalomyelitis (EAE)-induced group; △, EAE-induced and swimming exercise group; ■, EAE-induced and interferon-β-treated group. ^*P<0.05 compared with the control group. ^#P<0.05 compared with the EAE-induced group.

Fig. 3.

Motor functions and grip strength. (A) Motor coordination in the rotarod test. ●, control group; □, experimental autoimmune encephalomyelitis (EAE)-induced group; △, EAE-induced and swimming exercise group; ■, EAE-induced and interferon (IFN)-β-treated group. (B) Balance in the vertical pole test. (C) Muscle strength in the grip strength test. CON, control group; EAE, EAE-induced group; EAE-swim, EAE-induced and swimming exercise group; EAE-IFN-β, EAE-induced and IFN-β-treated group. ^*P<0.05 compared with the control group. ^#P<0.05 compared with the EAE-induced group.

Fig. 4.

Expression of pro-inflammatory cytokines and inflammatory mediators. (A) Expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the lumbar spinal cord tissue. (B) Expression of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lumbar spinal cord tissue. CON, control group; EAE, experimental autoimmune encephalomyelitis (EAE)-induced group; EAE-swim, EAE-induced and swimming exercise group; EAE-IFN-β, EAE-induced and IFN-β-treated group. IFN, interferon. ^*P<0.05 compared with the control group. ^#P<0.05 compared with the EAE-induced group.

Fig. 5.

Demyelination score and expression of nerve growth factor (NGF), myelin basic protein (MBP), and proteolipid protein (PLP). (A) Expression of demyelination in the lumbar spinal cord tissue. □ means demyelination evaluation site. The scale bar represents 50 μm (left) and 200 μm (right). (B) Demyelination score in each group. (C) Expression of NGF in the lumbar spinal cord tissue. (D) Expression of MBP in the lumbar spinal cord tissue. (E) Expression of PLP in the lumbar spinal cord tissue. CON, control group; EAE, experimental autoimmune encephalomyelitis (EAE)-induced group; EAE-swim, EAE-induced and swimming exercise group; EAE-IFN-β, EAE-induced and IFN-β-treated group. ^*P<0.05 compared with the control group. ^#P<0.05 compared with the EAE-induced group.