中国生物工程杂志

Objectiive:The present study was designed to explore whether overexpression of human wild α-synuclein in rat brain caused selective dopaminergic neuron loss in substantia nigra and aimed to find out a new method to make a rat model of Parkinson’s disease (PD). Methods:The human wild α-synuclein gene was induced into the rat brain by AdenoAssociated Virus (AAV) vector. The overexpression of α-synuclein was detected by realtime PCR. The behavior of rats were recorded every 4 weeks after the viral particle injection. TH immunohistochemistry were performed at 4, 8, 12 and 16 weeks post-injection as well as the dopamine (DA), 3,4-dihydroxypheny lacetic acid (DOPAC) of striatum were determined by high performance liquid chromatography coupled with electrochemical detection. Results:Realtime PCR results revealed a significant overexpression of α-synuclein in the injected hemisphere. By 8 weeks post injection, a significant loss of the dopaminergic neurons was observed. 34% of the dopaminergic neurons were lost after 12 weeks, and about 60% cells loss after 16 weeks. The DA and DOPAC levels in the striatum decreased about 15% 12 weeks after injecting viral particle carried α-synuclein gene and 30% decreased after 16 weeks. The AAV-α-synuclein-treated rats developed a type of motor impairment, i.e., head position bias, compatible with this magnitude of nigrostriatal damage. Conclusion:All the results showed that overexpression of human wild α-synuclein caused selective dopaminergic neuron loss and mimic a symptom of human PD in rats. This may be a new methed to make rat PD model which can offer new opportunities for the study of pathogenetic mechanismsand exploration of new therapeutic targets of particular relevance to human PD.