| Objective:To verify that aerobic exercise can improve the exercise and non-motor symptoms of PD,to analyze the differences in the expression of miRNAs in the circulation of PD patients before and after aerobic exercise,to find the differentially expressed miRNAs involved in regulating the related signaling pathways that are beneficial to PD,and to analyze the related mechanisms of aerobic exercise improving motor and non-motor symptoms in PD patients based on related pathways.Methods:(1)Aerobic exercise intervention:15 PD patients who were treated in the outpatient department of neurology of the First Hospital of Jilin University were selected.Taking themselves before and after exercise as the control,the patients received aerobic exercise intervention for a period of 4 weeks.The motor and non-motor symptoms of PD patients were evaluated by scales at the baseline,during the exercise,after exercise intervention,and at two-week follow-up after exercise.(2)Enrichment analysis of signal pathways of differentially expressed miRNA:before exercise and 4 weeks after exercise,we collected serum samples of 5 PD patients whose clinical symptoms most obvious improved to examine the expression of miRNAs.Next,we predicted the target genes of exercise-induced differential miRNAs,and analyzed their functions and signaling pathways,(3)Use SHSY5Y cells to verify the effect of exercise intervention:The SHSY5Y cells were intervened with the serum of PD patients at baseline(BL)and post-exercise(EX),and we set up healthy controls(HC)and negative controls(FBS)to validate the role of aerobic exercise-induced serum components in dopaminergic cell lines by measuring SHSY5Y cell activity and axonal growth.Results:(1)After 4 weeks of aerobic exercise,the scores of UPDRS-Ⅲ(open phase),MoCA and PDQ-39 in PD patients were significantly improved compared with baseline,and the difference was statistically significant(P<0.05).(2)After 4 weeks of aerobic exercise intervention,10 miRNAs in the serum of PD patients were significantly up-regulated by exercise,and 25 were significantly downregulated(P<0.05).According to the target gene prediction,and gene function and pathway enrichment analysis,we found that the axon guidance pathway was significantly regulated by differential miRNAs(P<0.05).(3)After SHSY5Y was incubated in groups,the cell activity of EX group was higher than that of BL group,although it did not reach the level of HC group,the difference between groups was not statistically significant.(4)After SHSY5Y was incubated in groups,compared with the HC group,the axonal growth of the BL group was inhibited,and the axonal length of the EX group was significantly longer than that of the other groups,and the difference was statistically significant(P<0.01).Conclusions:(1)4-week aerobic exercise significantly improved motor symptoms and non-motor symptoms(cognitive function and quality of life)in PD patients.(2)Aerobic exercise changed the expression level of miRNAs in serum of PD patients.According to target gene prediction and gene function and signaling pathway analysis,differential miRNAs were enriched in axon guidance pathways,suggesting that aerobic exercise-induced miRNAs play a beneficial role in PD by targeting the axon guidance pathway.(3)The scrum of PD patients after aerobic exercise has a tendency to promote cell activity,suggesting the role of aerobic exercise-induced serum in anti-apoptosis.(4)Serum of PD patients after aerobic exercise promoted cell axonal growth,combined with the analysis of exercise-induced differential miRNAs,it suggests that that aerobic exercise may target axon guidance pathways by regulating serum miRNAs to promote axonal growth. |
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