Study On The Mechanism Of Improving The Behavior Of Levodopa Induced Dysfunction Rats By Regulating The Expression Of Dopamine D3 Receptor By Chronic High Frequency Electrical Stimulation Of The Medial Part Of The Pallid Sphere(GPi DBS)

Background:Parkinson’s disease is a common degenerative disease of the central nervous system in the elderly,which seriously affects the daily exercise ability and living standard of patients.At present,it is the first choice to take levodopa as a supplement for dopamine in clinical treatment.At the early stage of treatment,levodopa has a good therapeutic effect.However,long-term use of levodopa will cause patients to have involuntary movement symptoms similar to chorea,that is,Levodopa-induced Dyskinesia.Now in clinical surgical treatment,high-frequency electrical stimulation of the medial part of the globus pallidus can be selected to relieve the symptoms of patients with dyskinesia.At the same time,basic research has found that the overexpression of D3R is positively correlated with the severity of LID.Therefore,this study is mainly to explore the mechanism of high frequency electrical stimulation of the medial part of the globus pallidus to regulate the dopamine D3 receptor in alleviating the involuntary motor symptoms of the rats with Levodapa-induced dyskinesia.Method:We made a model of Parkinson’s disease by injecting the prepared 6-hydroxydopamine hydrobromide solution into the right brain of the rats with a microinjector under the operation of a stereotactic device to damage the medial forebrain tract area,After 2 weeks of operation,the rats were injected with the prepared apomorphine solution for rotation induction experiment and open field experiment to analyze the difference in motor ability of the rats before and after the model establishment,and to determine whether the rats were successful in PD model establishment.Then,the stimulation electrode was implanted in the globus pallidus(GPi)of the right brain of the Parkinson’s disease rats that were successfully modeled,and then the PD rats with the electrode were induced to have LID-related involuntary movement symptoms by intraperitoneal injection of the mixed levodopa and benzylhydrazine solution,Then,the right GPi of the rats was given a constant high-frequency electrical stimulation of a specific wavelength through the master-9 pulse stimulator to observe the behavioral changes and differences of the LID rats under the state of electrical stimulation and false stimulation,and the improvement of LID behavior was analyzed through the AIM score for statistical analysis.After 21 days of administration and deep brain stimulation in SD rats,the brain of LID rats was perfused to make paraffin tissue sections.At the same time,the expression of dopamine D3 receptor(D3R)in striatum was observed by immunofluorescence test.Results:Through the intervention of chronic high-frequency electrical stimulation of the inner part of the pallidus,the non autonomous motor symptoms of LID rats in the DBS group were significantly improved compared to those in the sham stimulation group.The AIMs score was significantly reduced,and the duration of dyskinesia in LID rats in the DBS group was also significantly shortened.Compared to acute GPi DBS,chronic GPi DBS can significantly improve the behavior of LID rats and reduce AIM scores.The immunofluorescence experiment found that the expression of D3R in the striatum of LID rats treated with GPi DBS was significantly lower than that of sham stimulated LID rats and LID rats.Solution:High frequency electrical stimulation of the medial part of the chronic pallidus can improve the involuntary motor symptoms and duration of LID rats by down-regulating the expression of D3R receptor in the striatum.