The Effects Of Aerobic Exercise On Synaptic Plasticity MAPK/ERK Pathway In Striatum Of 6-OHDA Parkinson’s Disease Rats

Objective:The experimental subjects selected in this study were SD rats of 3 months old.The aerobic exercise was used as an intervention to explore the synaptic plasticity and MAPK/of aerobic exercise in6-OHDA Parkinson’s（PD）rats.The impact of the ERK pathway.Through the synaptic plasticity of the striatum and the changes of the MAPK/ERK pathway,it provides experimental theoretical basis for the clinical treatment of PD.Methons:Eighty SD rats were selected and divided into 4 groups according to the principle of random distribution.They were SED（Saline control group,n=12）and saline exercise group EX（Saline exercise group,n=20）.);Parkinson sedentary group（n=24）and Parkinson exercise runner group（n=24）in the Parkinson Quiet Group,in reference to the Bedford modelling program and the combination group^[65]Based on the previous study,the following rat exercise program was designed.First 3days of adaptive training（speed is 10m/min,exercise time is 10min on the first day,exercise time is 20min on the second day,exercise time is25min on the third day,and the slope is 0°）.After a day off,formal training begins.Animals are specially selected to feed rat plastic products,stainless steel cover and plastic water absorption bottle,fed by national standard animal feed,free diet,and the temperature is maintained at 24°C²6°C.Eight weeks of aerobic training,five days a week,two days off.Aerobic exercise was completed for eight weeks,and one week of modeling was performed.6-OHDA was injected into the right side of the rat striatum,and normal saline was injected into the right side of the rat striatum.After two weeks of rehabilitation exercise and rotation test evaluation,four groups of rats were tested for striatum after 24 hours of the last rotation experiment.HE staining,gene sequencing,immunohistochemistry and RT-PCR were used to detect synaptic plasticity in the striatum and related genes of the MAPK/ERK pathway.Immunohistochemical detection of protein:TH,a-synuclein,BDNF expression;RT-PCR detection of genes:SYN1,ALDH18a1,ALDH2,MAPK7,ERK1/2 mRNA expression.Results:1)The results of neurobehavioral rotation experiments showed that the power of SED-PD was 75%and the power of EX-PD was 58.3%.The SED-PD group had more successful samples than the EX-PD group,and the results were significantly different（Ρ<0.05）.2)HE staining:In the SED group and the EX group,the number of neurons was clear and there was a clear dense band;the SED-PD group had fewer neurons,and many glial cells appeared;EX-PD The group clearly showed improvement.3)Gene sequencing results showed that the gene sequencing results in the PD rat striatum up-regulated by 2 or more genes:ALDH18a1,MAPK7,transcription factor Nupr1,heat shock protein 90-αand nuclear heterogeneous ribonucleoprotein 11 known mRNAs;while the genes that exercised 2-fold or more down-regulation of the striatum of PD rats were14 known mRNAs such as transcription factor Tfap2d and vascular endothelial growth factor VEGFR.Through GO and KEGG bioinformatics analysis,ALDH and MAPK are the target genes of this experiment.4)Immunohistochemistry results showed that 1TH protein was abundantly expressed in the cytoplasm and nucleus of striatum,and the distribution was relatively concentrated,and the color was reddish brown.Compared with the SED in the quiet group,the TH protein in the EX group was up-regulated（P<0.05）,and the EX-PD group was significantly（P<0.01）.Compared with the saline group,the SED-PD group and the EX-PD group were significantly expressed（p<0.01）.Compared with the EX-PD group,the TH protein in the EX-PD group was significantly up-regulated in the SED-PD group（p<0.01）.2 The expression ofα-synuclein in the cytoplasm of the striatum was brown,and the SED group accumulated a lot,and the EX-PD group was significantly reduced.Compared with the quiet group SED,the expression ofα-synuclein protein in the EX group was not obvious,and theα-synuclein in the EX-PD group was significantly decreased（P<0.01）.The expression of SED-PD group was significantly up-regulated in SED group compared with SDE-PD group（P<0.05）.Compared with the EX-PD group,the expression ofα-synuclein protein in the EX-PD group was significantly decreased in the SED-PD group（P<0.01）.3 Compared with SED saline,the expression of BDNF in SED-PD group was significantly decreased（P<0.01）;the implementation of aerobic exercise significantly increased the expression level of BDNF,compared with the corresponding quiet group,the EX group and the EX-PD group.The expression of BDNF was significantly increased（P<0.01）.It indicated that PD decreased the expression of BDNF in rat striatum and showed significant expression（P<0.01）.5)RT-PCR results showed that:1 Compared with the SED saline group,the SYN1 expression level in the SED-PD group was significantly decreased（P<0.01）;the implementation of aerobic exercise significantly increased the SYN1 expression level,and corresponding Compared with the static group,the expression level of SYN1 in the EX group and the EX-PD group was significantly increased（P<0.01）.However,compared with the EX saline group,the expression level of SYN1 in the EX-PD group was significantly decreased（P<0.05）.2 Compared with the SED saline group,the expression level of ALDH18A1 in SED-PD was significantly increased（P<0.01）;the implementation of aerobic exercise significantly increased the expression level of ALDH18A1,compared with the corresponding quiet group,EX group and EX-PD The expression level of ALDH18A1 was significantly increased in the group（P<0.01）.Compared with the EX saline group,the expression level of ALDH18A1 in the EX-PD group was significantly increased（P<0.01）.Further,the effect of exercise on the expression level of ALDH2 in the rat model of PD model was observed.The aerobic exercise significantly increased the expression level of ALDH2.Compared with the corresponding quiet group,the EX group and the EX-PD group significantly increased the expression level of ALDH2.（P<0.01）;ALDH2 expression level was significantly increased in the EX-PD group compared with the EX saline exercise group.3 Compared with the SED saline group,the MAPK7 expression level in the SED-PD group was slightly increased（P>0.05）;the aerobic exercise significantly increased the MAPK7 expression level,compared with the corresponding quiet group,the EX group and The expression level of MAPK7 in the EX-PD group was significantly increased（P<0.01）.Compared with the EX saline group,the expression level of MAPK7 in the EX-PD group was significantly increased（P<0.05）.In view of the downstream gene ERK1/ERK2 of MAPK7,the effect of exercise on the expression level of ERK1 in the striatum of PD model rats was obtained.The aerobic exercise significantly increased the expression level of ERK1/ERK2,except for the physiological saline exercise group ERK2.Compared with the corresponding quiet group,the expression level of ERK1 in the EX group and the EX-PD group was significantly increased,and the expression group P<0.05,but the expression level in the EX-PD group was not significantly increased（P>0.05）;The expression level of ERK2was slightly decreased in the group,but the expression level of ERK2was significantly increased in the EX-PD group（P<0.01）.Conclusions:Aerobic exercise up-regulates the expression of ALDH in the presynaptic membrane,up-regulates the MAKP7-initiated MAPK pathway to up-regulate ERK1/2,promotes the expression of TH and SYN1,inhibits the accumulation ofα-synuclein,thereby affecting synaptic formation and conduction,and improving PD synaptic plasticity,delaying neuro regression improves the development of PD lesions.