Overexpression of ?-Synuclein Gene Caused Dopaminergic Neuron Damage in Substantia Nigra of Rats
- VernacularTitle:AAV介导的?-synuclein基因过表达致多巴胺能神经元损伤——一种制作轻度帕金森病大鼠模型的新方法
- Author:
Ling-Ling LU
;
Ai-Xia ZHOU
;
Hui YANG
;
- Publication Type:Journal Article
- Keywords:
Parkinson's disease ?-Synuclein/NACP Animal model
- From:
China Biotechnology
2006;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Objectiive:The present study was designed to explore whether overexpression of human wild ?-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 ?-synuclein gene was induced into the rat brain by Adeno-Associated Virus(AAV) vector.The overexpression of ?-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 ?-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 ?-synuclein gene and 30% decreased after 16 weeks.The AAV-?-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 ?-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.
