Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons

• Published in: Neural regeneration research 2014-05, Vol.9 (9), p.951-958
• Main Authors: Tai, Yunchun, Chen, Ling, Huang, Enping, Liu, Chao, Yang, Xingyi, Qiu, Pingming, Wang, Huijun
• Format: Article
• Language: English
• Subjects: Apoptosis; Dopamine; Dopaminergic mechanisms; Genetic aspects; Methamphetamine; Nerve proteins; Neural circuitry; Neurons; Neurotoxicity; Nitrogen; Oxidative stress; Physiology; Polyclonal antibodies; Properties; Proteins; Reactive oxygen species; Research and Report; α-突触核蛋白; 一氧化氮合酶; 保护作用; 多巴胺能神经元; 实验大鼠; 甲基苯丙胺; 神经毒性; 超氧化物歧化酶活性
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.133146

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 of α-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.