Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons
Yunchun Tai
Ling Chen
Enping Huang
Chao Liu
Xingyi Yang
Pingming Qiu
Huijun Wang
摘要：The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson’s disease. In the present study, α-synuclein knockdown rats were created by injecting α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental rats. At 2 weeks post-injection, the rats were injected intraper-itoneally with methamphetamine to establish the model of Parkinson’s disease. Expression ofα-synuclein mRNA and protein in the right striatum of the injected rats was significantly down-regulated. Food intake and body weight were greater in α-synuclein knockdown rats, and water intake and stereotyped behavior score were lower than in model rats. Striatal dopamine and tyrosine hydroxylase levels were significantly elevated in α-synuclein knockdown rats. Moreover, superoxide dismutase activity was greater in α-synuclein knockdown rat striatum, but the levels of reactive oxygen species, malondialdehyde, nitric oxide synthase and nitrogen monoxide were lower compared with model rats. We also found that α-synuclein knockdown inhibited metham-phetamine-induced neuronal apoptosis. These results suggest that α-synuclein has the capacity to reverse methamphetamine-induced apoptosis of dopaminergic neurons in the rat striatum by inhibiting oxidative stress and improving dopaminergic system function.
机标关键词：dopaminergic neuronsreactive oxygen speciestyrosine hydroxylaseneuronal apoptosisnitrogen monoxideoxidative stresssystem functionwater intake
资助基金：This study was supported by the National Natural Science Foundation of China, (No.81072506)
论文发表日期：2014-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 951-958 )
英文信息