Neuroprotective Mechanisms Of Optimized DNA Vaccine In A MPTP Model Of Parkinson’s Disease

Objective:To explore the neuroprotective mechanisms of optimized DNA vaccine in a MPTP model of Parkinson’s disease. Methods:C57BL/6 mice were randomly divided into normal control group, empty plasmid group, PBS group, optimized DNA vaccine group. The anterior tibial muscles of mice hind leg were respectively injected with PBS, empty plasmid, PBS, and pVAX1-IL4/SYN-B. Then chronic MPTP mouse PD were built by intraperitoneal injection of MPTP, while the normal control group injected the same volume of PBS. The behavior changes were observed, the expression of tyrosine hydroxylase (TH) in striatum of mice were detected by Western blot and immunohistochemistry, the activation of microglia were detected by immunohistochemistry,and the expressions of Glial cell line-Derived Neurotrophic Factor(GDNF),Brain derived neurotrophic factor(BDNF),Immunoglobulin G(IgG) were detected by Western blot. Results:1.The behavioral deficits in optimized DNA vaccine group was improved significantly, compared with PBS group and empty plasmid group (P<0.05)2.Western blot and immunohistochemistry showed the expression level of TH in striatum of mice of PBS groups and empty plasmid groups were reduced significantly, compared with normal control group (P< 0.05). The expression level of TH in striatum of mice of optimized DNA vaccine groups were increased significantly, compared with PBS group or empty plasmid group (P<0.05)3.Western blot showed the expression level of GDNF,BDNF and IgG of mice of optimized DNA vaccine groups were increased significantly, compared with PBS group and empty plasmid group (P<0.05)4.Immunohistochemistry showed that the microglia in optimized DNA vaccine group become "activated" compared with normal control group,PBS group or empty plasmid group. Conclusions:The present study showed that hα-syn antibodies(IgG) generated in vaccinated mice can traffic into the CNS, target and aid in clearance of extracellular α-syn proteins by microglia.Moreover, Optimized DNA vaccine has neuroprotective effects in chronic MPTP Parkinson’s disease mice by increasing the expression of neurotrophic factor GDNF and BDNF in striatum.