| AIM Parkinson 's disease(PD)is the world 's second-largest neurodegenerative disease and elderly chronic disease.The symptoms of PD patients show behavioral dysfunction and cognitive decline.Physical exercise has been widely used in the clinical treatment of PD patients,and has achieved positive results in improving the behavioral functions of PD patients and model animals.However,it is unclear how exercise affects the abnormal expression of Parkinson's disease-causing protein ?-synuclein and the neuronal apoptosis it causes.Through 8-week treadmill exercise intervention,the ?-syn expression and dopaminergic neuron apoptosis in the substantia nigra of PD mice were observed.To explore the effect and mechanism of treadmill exercise on the apoptosis of dopaminergic neurons caused by the abnormal aggregation of ?-syn protein.METHODS 32 male C57BL/6J mice were randomly divided into 4 groups: saline group(S),saline+exercise group(SE),MPTP group(M),MPTP+exercise group(ME),n=8.The PD model was constructed by intraperitoneal injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).The mice in the control group were injected with the same dose of normal saline.After the PD modeling is completed,an 8-week treadmill exercise is performed.Rotarod?Gait analysis and Beam Balance Test to detect mice motor ability;Tail suspension test and Forced Swimming Test to detect depression and anxiety in mice;High maze and open field experiments detect the desire of mice to explore in unfamiliar environments.Sacrifice the mice after the behavioral test.Detection and expression of ?-syn,?-syn,dopaminergic neurons,mitochondrial fusion protein MFN2,mitochondrial fission protein DRP1,mitochondrial autophagy protein PINK1,Parkin,mitochondrial membrane protein TOM40,apoptotic proteins BAX,cleared-caspase3 and AIF,antiApoptosis protein BCL-2.RESULTS(1)Compared with the S group,the SE group has no significant difference(P>0.05),but the rotarod time in the M group is reduced,and the balance beam passing time in the M group is increased,there is a significant difference(P<0.05 or P<0.01);compared with the M group,the rotarod time in the ME group is increased,the balance beam passing time in the ME group is decreased,and there is a significant difference(P<0.05).(2)In the forced swimming experiment,compared with the S group,the SE group has no significant difference(P>0.05),but the fast swimming time in the M group was significantly reduced(P<0.01);compared with the M group,the fast swimming time in the ME group forced swimming experiment was significantly increased(P<0.05).(3)Compared with the S group,the M group's open arm activity time and the range of activity in the open field experiment decreased significantly(P<0.05 or P<0.01);compared with the M group,the ME group's open arm activity time and the range of activity in the open field experiment increased significantly(P<0.05).(4)Compared with group S,the SE group has no significant difference(P>0.05),but the expression of ?-syn in group M was significantly increased(P<0.01),the expression of ?-syn was significantly decreased(P<0.05),and the number of dopaminergic neurons was significantly reduced(P<0.01);Compared with group M,the expression of ?-syn in the ME group was significantly reduced(P<0.05),the expression of ?-syn was significantly increased(P<0.05),and the number of dopaminergic neurons was significantly increased(P<0.01).(5)Compared with group S,the SE group has no significant difference(P>0.05),but the expression of mitochondrial fusion protein MFN2 in group M was significantly decreased(P<0.05).Compared with group M,the expression of mitochondrial fusion protein MFN2 in group ME was significantly increased(P<0.05),There was no significant difference in protein DRP1 expression(P>0.05).(6)Detect the expression of mitochondrial autophagy protein PINK1,compared with group S,the SE group was significantly increased(P<0.05),M group was not significantly different(P>0.05);compared with M group,ME group was significantly increased(P<0.05).Mitochondrial autophagy protein Parkin expression,compared with the S group,the SE group was significantly increased(P<0.05),M group was significantly increased(P<0.05);compared with the M group,the ME group was significantly increased(P<0.05)).(7)Detect the expression of TOM-40,compared with group S,the SE group has no significant difference(P>0.05),the expression in group M was significantly reduced(P<0.05).Compared with group M,the expression in group ME was significantly increased(P<0.05).(8)Compared with group S,the SE group has no significant difference(P>0.05),but the expressions of apoptosis factors BAX,cleared-caspase3 and AIF in group M were significantly increased(P <0.05 or P <0.01);compared with group M,the expression of BAX,cleared-caspase3 and AIF in ME group was significantly reduced(P <0.05).Compared with group S,the SE group has no significant difference(P>0.05),but the expression of anti-apoptotic protein Bcl-2 in group M decreased significantly(P <0.05);compared with group M,the expression of Bcl-2 protein in group ME increased significantly(P <0.05).CONCLUSION(1)Aerobic exercise increases the expression of ?-Syn protein in the brain of PD mice,inhibits the abnormal aggregation of ?-syn protein,and alleviates the apoptosis of dopaminergic neurons.(2)Aerobic exercise can play a positive role in protecting neurons by reducing the abnormal expression of ?-syn protein in the brain of PD mice,enhancing mitochondrial function,inhibiting apoptosis. |
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