Objective   To explore the neuroprotective effects of optimized human α-synuclein DNA vaccine on dopaminergic neurons after acute neurotoxin damage.    Methods   Totally 24 C57BL/6J mice were randomly divided into 3 groups: the optimized human α-synuclein (α-syn) DNA vaccine group (pVAX1-Igk-hαS1-140)

the empty plasmid group (pVAX1)

and the PBS group. Before the immunizing of mice every time

anterior tibial muscles of mice hind legs were respectively injected with 50 μl  0.5% bupivacaine unilaterally. In 72 h later

those mice were injected unilaterally at t

he same site and in the same depth with 50 μl corresponding agents. The immunization was given once every three weeks for totally 3 times. Two weeks after the last immunization

those mice of pVAX1-Igk-hαS1-140 group and pVAX1 group were intraperitoneally injected with 250 mg/kg probenecid followed by injection with MPTP (25 mg·kg

-1

·d

-1

×5 d

s.c.; dissolved in 0.9% NS) in the back

and those mice of PBS group were injected with the same volume of PBS. The mice were sacrificed on the second day after last MPTP injection and their brain was taken out for immunofluorescence and immunostaining. From the next day after the last immunization injection to the day of death

the behavior of all mice were observed by pole testing.    Results   Compared with empty plasmid group

the scores of pole test of pVAX1-Igk-hαS1-140 DNA vaccine group was decreased with significant differences (P0.05). Compared with PBS group

the scores of pole test were increased but there was no significance differences (P0.05). Compared with empty plasmid group

the number of tyrosine hydroxylase-positive cells of pVAX1-Igk-hαS1-140  DNA vaccine group was increased and that of apoptotic cells was decreased significantly (P0.05). At the same time

the number of α-synuclein expression-positive cells was decreased for a little

but there was no statistically significant difference (P0.05). Compared with PBS group

the number of tyrosine hydroxylase-positive cells of empty plasmid group was decreased and that of apoptosis cells was increased significantly (P0.05). At the same time

the number of α-synuclein-positive cells was increased significantly (P0.05).    Conclusion   The optimized DNA vaccine improves the behavior of mice with Parkinson’s disease

and at the same time it plays a positive role in strengthening immunogenicity and exerting neuroprotective effects on dopaminergic neuron against acute neurotoxin damage.