Immunotherapeutic effects of optimized alpha-synuclein DNA vaccine immunize MPTP inducing on chronic mouse model of Parkinson's disease
AIM: To investigate the neurological effects of immune protection of highly secretion of optimized human alpha-synuclein (human alpha-synuclein, ha-syn) DNA vaccine (pVAX1-Igk-hαS1-140) immunizes MPTP inducing on chronic mouse model of Parkinson's disease. METHODS: All of mice were administrated with the neurotoxin MPTP[25 mg/(kg · d) MPTP, twice one week, accumulative total 10 times] so that gaining the chronic mouse model of Parkinson's disease (PD), those mice were randomly divided into three groups: The optimized high secreted ha-syn DNA vaccine(pVAX1-Igk-hαS1-140), the full sequence ha-syn DNA vaccine (pVAX1-hαS1-140), the control group with PBS. Before of mice were immunized every time, the two-leg site of mice leg anterior tibial muscles were respectively injected for 50 μL unilaterally with the 0.5% bupivacaine. After 72 h, those mice were respectively injected for 50 μL unilaterally with the pVAX1 -Igk-hαS1-140, pVAX1-hαS1-140, the saline solution in the same site and depth. One time every 3 weeks, accumulative total 3 times. To observe the behavioral changes after last immunization for 2 weeks interval. Finally, we remove the brain and observe the expression of a-syn and TH-positive counts in substantia nigra about 2 weeks after the last immunization injection. RESULTS: Compared to the PBS group, the scores of pole behavior were improved significant of the optimized ha-syn DNA vaccine group (pVAX1-Igk-hαS1-140) and the ha-syn DNA vaccine group (pVAX1-hαS1-140), there was significant difference(P ＜ 0.05), but there was no significant difference between the optimized ha-syn DNA vaccine group(pVAX1-Igk-hαS1-140) and the ha-syn DNA vaccine group(pVAX1-hαS1-140). Compared to the PBS group and the ha-syn DNA vaccine group (pVAX1-hαS1-140), the pVAX1-Igk-hαS1-140 DNA vaccine group can increase the TH positive cells 20%-68% (P ＜ 0.05), and decrease the a-syn expression in substantia nigra 15%-45% (P ＜ 0.05). CONCLUSION: We conclude that the optimized ha-syn DNA vaccine group(pVAX1-Igk-hαS1-140) have much more effects to improve the mice behavior of Parkinson's disease, and enhance immunogenicity. It can promote the repair of damage of the dopaminergic neuron in substantia nigra cells, and has a better immunization effects to Parkinson's disease.
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NSTL
万方数据
维普
