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Publication : Increased sensitivity to MPTP in human alpha-synuclein A30P transgenic mice.

First Author  Nieto M Year  2006
Journal  Neurobiol Aging Volume  27
Issue  6 Pages  848-56
PubMed ID  16006012 Mgi Jnum  J:108858
Mgi Id  MGI:3625207 Doi  10.1016/j.neurobiolaging.2005.04.010
Citation  Nieto M, et al. (2006) Increased sensitivity to MPTP in human alpha-synuclein A30P transgenic mice. Neurobiol Aging 27(6):848-56
abstractText  In addition to genetic factors, environmental factors have long been suspected to contribute to the pathogenesis of Parkinson's disease (PD). We investigated the possible interaction between genetic factors and neurotoxins by testing whether alpha-synuclein A30P Tg5093 transgenic mice show increased sensitivity to secondary toxic insults like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone. While sensitivity to chronic treatment with rotenone was not enhanced in the Tg5093 line, chronic treatment with 80 or 150 mg/kg MPTP resulted in increased deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) positive neurons and striatal dopamine (DA) levels in Tg5093 mice when compared to non-transgenic littermate controls. Thus, the results of this study demonstrate a role for the overexpression of mutant human alpha-synuclein A30P in increased vulnerability of DA neurons to MPTP.
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