The Research Of α-synuclein On The Expression Changes Of Dopamine Receptor

OBJECTIVE: Parkinson’s disease（PD）is a common neurodegenerative disease,and the prevalence of older people over the age of 65 is about 2%.The typical clinical features of PD are dyskinesia such as bradykinesia,resting tremor,and muscle stiffness.And the reason of these symptoms is that the lack of dopamine（DA）neurotransmitters in the striatum caused by the loss of DA neurons in the substantia nigra.Another pathological hallmark of PD is the inclusion of neuronal inclusions,namely lewy bodies（LBs）and lewy neurites（LNs）,whose main components are abnormally modified and aggregatedα-synuclein（α-syn）.Studies have shown that there is an interaction between the abnormal aggregation of α-syn and the loss of DA neurons in the two main pathological features of PD,and thus will further aggravate the accumulation ofα-syn and selective death of DA neurons.The physiological role of DA is mediated by the dopamine receptor（DR）.Currently known to play a major role in exercise control are DA receptor 1（D1DR）and DA receptor 2（D2DR）,but the role of α-syn in DR has not been elucidated.Therefore,this study aimed to investigate whether abnormal aggregation and modification of α-syn can alter the expression of D1 DR or D2 DR.METHODS: The recombinant human α-syn was incubated and purified to prepare α-syn aggregates;the optimal amount of α-syn aggregates injected into the striatum was determined by cytotoxicity detection;The inclusion criteria of the experimental mice were determined according to the baseline results of the behavioral test,including climbing rod experiments,balance bar experiments,and open field experiments;The model of PD mice was established by stereotaxic injection of α-syn aggregates into the striatum;After 30 days of striatum injection,the behavioral state of the mice was assessed by behavioral testing.And detected by α-syn in the substantia nigra,phosphorylated α-syn（Phosphorylation-α-syn,P-α-syn）,tyrosine hydroxylase（TH）,D1 DR and D2 DR by protein immunoblotting and immunofluorescence.RESULTS: After the striatum was injected with α-syn aggregates for 30 days,behavioral tests showed that mice injected with α-syn aggregates increased their time through the climbing rod and balance bar,and slowed the movement speed decreased and the trajectory decreased in the open field.At the same time,the expression of α-syn and P-α-syn increased,and the expression of TH decreased in mice injected with α-syn aggregates,suggesting the successful establishment of the PD mouse model.On the basis of this model,protein immunoblotting and immunofluorescence results showed that D1 DR expression was decreased,while D2 DR expression was not significantly changed.Conclusion: Intracerebral injection of α-syn aggregates can establish the PD mouse model with behavioral disorders and loss of DA neurons.In this model,the expression of D1 DR in the substantia nigra is reduced.