Exercise Training Improves Cuprizone-induced Behavioral Disorders And Demyelination In Mice And Its Related Mechanisms

Background:Demyelinating diseases of the central nervous system,such as multiple sclerosis,with myelin destruction and oligodendrocyte apoptosis as the main pathological features,can cause serious neurological diseases,which greatly affect the quality of life of patients.More and more studies are currently underway to develop its pathogenesis and treatment.Oxidative stress is one of the important mechanisms of demyelinating disease.Exercise has been shown to improve cognitive,motor and other behaviors in MS patients,but the underlying mechanisms are still not fully elucidated.Objectives:Assessing the effects of exercise training on cognitive,anxiety and other behaviors of demyelinated mice can reduce demyelination and reduce oxidative stress.Methods:54 male 7-8 week old C57BL/6 mice were divided into 3 large groups:control group,model group and exercise group,with 18 mice in each group.The control group was given normal feed for 4 weeks without exercise;the model was given 0.3%Cuprizone mixed feed for 4 weeks without exercise;the exercise group was given 0.3%Cuprizone mixed feed for 4 weeks and treadmill training(0 Slope,running speed 12m/min,training 20min every day,every Saturday and Sunday).Three groups of mice were subjected to water maze test,rotating rod experiment,elevated plus maze test and weighing on the 0th,2nd and 4th weekends respectively.Then,brain specimens were taken for MBP immunohistochemistry in the corpus callosum to evaluate myelin loss.,and ELISA analysis of ROS,Nrf2 protein,HO-1 protein expression levels to assess oxidation and antioxidant response.Results:Compared with the control group,the model mice showed a significant increase in anxiety behavior(P<0.05)and a significant decrease in body weight(P<0.05)from the second week.Compared with the model group,the exercise group mice were at the 4th week.The anxiety behavior was significantly improved(P<0.05),and the body weight was significantly increased at the 2nd week(P<0.05).There was no significant difference in learning and memory ability and motor coordination ability between the three groups(P>0.05).At week 2 and week 4,the MBP protein,ROS,Nrf2 protein and HO-1 protein in the exercise group were significantly lower than those in the model group(P<0.05).Conclusion:Exercise training can alleviate the demyelination of Cuprizone-induced demyelinated mice,improve the anxiety behavior of mice,increase the body weight of mice,and may be related to the reduction of oxidative stress damage caused by ROS,and the underlying mechanism is through Nrf2-ARE signaling pathway.Regulates oxidative stress,but further research is needed.