Department of Molecular & Clinical Pharmacology, Faculty of Medicine, ICBM, University of Chile, Santiago, Chile.
Neurotox Res. 2012 Aug;22(2):177-80. doi: 10.1007/s12640-012-9326-7. Epub 2012 Apr 12.
Parkinson's disease is a debilitating progressive neurodegenerative disorder that results from the loss of or damage to dopaminergic cells containing neuromelanin in the substantia nigra (SN). The underlying neurodegenerative mechanism(s), however, remain elusive. Aminochrome, the precursor of neuromelanin is an endogenous substance capable of inducing selective neurotoxicity to dopaminergic neurons in SN. Nicotine, on the other hand, may offer protective effects against dopaminergic cell damage induced by various neurotoxins including MPTP and salsolinol. In this study, we sought to determine whether nicotine may also protect against aminochrome-induced toxicity in SN derived RCSN-3 cells. Exposure of RCSN-3 cells to a combination of aminochrome (50 μM) and dicoumarol (50 μM) for 48 h induced approximately 70 % cell death. Pretreatment with nicotine, dose-dependently blocked this toxicity. The effects of nicotine in turn were dose-dependently blocked by mecamylamine, a non-selective nicotinic receptor antagonist. These results suggest involvement of nicotinic receptors in protective effects of nicotine against aminochrome-induced toxicity and provide further evidence for possible therapeutic effects of nicotine or nicotinic agonists in Parkinson's disease.
帕金森病是一种使人衰弱的进行性神经退行性疾病，是由黑质（SN）中含神经黑素的多巴胺能细胞的丧失或损伤引起的。然而，潜在的神经退行性机制仍不清楚。氨基酮，神经黑素的前体，是一种内源性物质，能够诱导 SN 中的多巴胺能神经元选择性神经毒性。另一方面，尼古丁可能对包括 MPTP 和 salsolinol 在内的各种神经毒素诱导的多巴胺能细胞损伤提供保护作用。在这项研究中，我们试图确定尼古丁是否也可以防止氨基酮诱导的 RCSN-3 细胞中的 SN 毒性。将 RCSN-3 细胞暴露于氨基酮（50 μM）和双香豆素（50 μM）的混合物中 48 小时会导致大约 70%的细胞死亡。用尼古丁预处理，可剂量依赖性地阻断这种毒性。尼古丁的作用反过来又被美加明（一种非选择性烟碱受体拮抗剂）剂量依赖性地阻断。这些结果表明烟碱受体参与了尼古丁对氨基酮诱导的毒性的保护作用，并为尼古丁或烟碱激动剂在帕金森病中的可能治疗效果提供了进一步的证据。
