Study On The Role Of Rapamycin In The Occurrence Of Calcium Ion Related Regulatory Enzymes In L-dopa-induced Dyskinesia

Objective The most useful treatment for Parkinson's disease is levodopa.It shows LID(L-dopa-induced dyskinesia)would appear if levodopa used by certain times.By inhibiting mTOR signal,it can significantly reduce LID but not hinder levodopa therapeutic effection of on PD,in which calcium-related regulatory enzymes play an important role in the mTOR signaling pathway,was investigated in this study.The calcium-related regulatory enzyme was inhibited by the mTOR signaling pathway in the striatum of rats with dyskinesia induced by levodopa.The expression reveals its role in LID and explores its mechanisms.Methods A total of 50 Sprague-Daewley(SD)male adult male rats were randomly divided into 5 groups with 10 in each group.There were 10 normal group(N group)and Parkinson's disease(PD)model.Group 10,10 groups with LID,10 rapamycin-treated group,10 in intervention group(R group),and 10 in rapamycin solvent control group(C group).Western blot analysis of striatum tissue of N group,PD group,LID group,C group and R group was performed to detect the phosphorylation sites of calcium-related regulatory enzymes(such as CaMK?,PKC,PP1,and PP2A).changement.Immunohistochemical technique was used to detect the changes of p-CaMK? in striatum.Results The expression of p-CaMK??-(Thr286)/CaMK??-(Thr286),SynapsinI(Ser603),MARCKS(Ser152),NMDAR,and PP-1 sites in the striatum of LID rats increased,and rapamycin intervention was observed.The expression levels of p-CaMK??-(Thr286)/CaMK??(Thr286),SynapsinI(Ser603),MARCKS(Ser152),NMDAR,and PP-1 sites in the R group were decreased(P<0.05).The expression levels of PP-2A and p-PKA/PKA did not change,and there was no statistical difference.Results of immunohistochemistry expression: Compared with group C,the p-CaMK? in group R decreased compared with group C(P<0.05).Compared with group C,the NMDAR in group R decreased compared with group C.Significance(P<0.05),PP-1 in group R decreased compared with group C,and the difference was statistically significant(P<0.05).Conclusions (1)The mTOR signaling pathway is closely related to the pathogenesis of LID in levodopa disorders.The mTOR inhibitor rapamycin is effective for the treatment of LID.(2)mTOR activation has a regulatory effect on synaptic levels in rat striatum,probably since the synaptic molecules CaMK?,NMDAR,MARCKS,PP1 subtypes of the phosphorylation of synaptic plasticity memory regulation,resulting in striatum Synapses in the area "pathological LTP" followed by LID.