BACKGROUND The therapeutic potential of induced pluripotent stem cells(iPSCs)for Parkinson’s disease(PD)has been demonstrated.Exercise can also modulate metabolism to improve motor dysfunction in PD patients.AIM To i...BACKGROUND The therapeutic potential of induced pluripotent stem cells(iPSCs)for Parkinson’s disease(PD)has been demonstrated.Exercise can also modulate metabolism to improve motor dysfunction in PD patients.AIM To investigate the therapeutic effect of exercise combined with iPSCs in a PD mouse model and explore the underlying mechanisms.METHODS In this study,we included 10 normal mice and 40 PD model mice,which were divided into five groups:The control group(n=10),the sedentary PD group(St group,n=10),the exercise PD group(E group,n=10),the iPSC-treated PD group(T group,n=10),and the combined exercise and iPSC-treated PD group(ET group,n=10).The T and ET groups received cell injection therapy,while the E and ET groups underwent an 8-week exercise intervention.After the intervention,behavioral tests were performed on mice from all groups.Serum levels of epinephrine(EPI)and nerve growth factor were measured,and the expression of Wnt1,Lmx1a,and other factors related to the Wnt signaling pathway in the midbrain of mice were assessed.RESULTS The motor ability of the T group was higher than that of the St group,but the difference was not significant.However,the protein and gene expression levels of Wnt1,Lmx1a,Neurog2,and TH in the T group were significantly higher than those in the St group(P<0.01).Compared with the T group,the motor ability of the E group was significantly enhanced(P<0.01),and the gene expression level of Wnt1 in the midbrain of the E group was significantly higher than that of the T group(P<0.05).The levels of EPI and nerve growth factor were increased in both the E and ET groups.Exercise can improve motor dysfunction in PD,increase EPI levels,and elevate Wnt1 levels.However,western blot results revealed no significant change in the TH level of the E group,which may be because exercise does not cause a noticeable change in the number of neurons.Compared with the St group,both the E and ET groups showed improved motor function(P<0.01).The results showed that compared with the St group,the protein and gene expression levels of Wnt1,Lmx1a,and Neurog2 were significantly increased in the E,T,and ET groups(P<0.05).Compared with the T and E groups,the protein and gene expression levels of Wnt1,Lmx1a,and Neurog2 were significantly increased in the ET group(P<0.05).CONCLUSION Exercise increases EPI levels,activates the Wnt signaling pathway throughβ2 receptors,enhances the Wnt1-Lmx1a regulatory loop,and promotes the differentiation of iPSCs into dopaminergic neurons,thereby increasing the number of neurons.展开更多
基金Supported by the Central Government Guides Local Science and Technology Development Funds,No.YDZX2022091General Program of Natural Sciences of Qilu Medical University,No.X24ZKQN03.
文摘BACKGROUND The therapeutic potential of induced pluripotent stem cells(iPSCs)for Parkinson’s disease(PD)has been demonstrated.Exercise can also modulate metabolism to improve motor dysfunction in PD patients.AIM To investigate the therapeutic effect of exercise combined with iPSCs in a PD mouse model and explore the underlying mechanisms.METHODS In this study,we included 10 normal mice and 40 PD model mice,which were divided into five groups:The control group(n=10),the sedentary PD group(St group,n=10),the exercise PD group(E group,n=10),the iPSC-treated PD group(T group,n=10),and the combined exercise and iPSC-treated PD group(ET group,n=10).The T and ET groups received cell injection therapy,while the E and ET groups underwent an 8-week exercise intervention.After the intervention,behavioral tests were performed on mice from all groups.Serum levels of epinephrine(EPI)and nerve growth factor were measured,and the expression of Wnt1,Lmx1a,and other factors related to the Wnt signaling pathway in the midbrain of mice were assessed.RESULTS The motor ability of the T group was higher than that of the St group,but the difference was not significant.However,the protein and gene expression levels of Wnt1,Lmx1a,Neurog2,and TH in the T group were significantly higher than those in the St group(P<0.01).Compared with the T group,the motor ability of the E group was significantly enhanced(P<0.01),and the gene expression level of Wnt1 in the midbrain of the E group was significantly higher than that of the T group(P<0.05).The levels of EPI and nerve growth factor were increased in both the E and ET groups.Exercise can improve motor dysfunction in PD,increase EPI levels,and elevate Wnt1 levels.However,western blot results revealed no significant change in the TH level of the E group,which may be because exercise does not cause a noticeable change in the number of neurons.Compared with the St group,both the E and ET groups showed improved motor function(P<0.01).The results showed that compared with the St group,the protein and gene expression levels of Wnt1,Lmx1a,and Neurog2 were significantly increased in the E,T,and ET groups(P<0.05).Compared with the T and E groups,the protein and gene expression levels of Wnt1,Lmx1a,and Neurog2 were significantly increased in the ET group(P<0.05).CONCLUSION Exercise increases EPI levels,activates the Wnt signaling pathway throughβ2 receptors,enhances the Wnt1-Lmx1a regulatory loop,and promotes the differentiation of iPSCs into dopaminergic neurons,thereby increasing the number of neurons.
