title: Increased sensitivity to MPTP in human alpha-synuclein A30P transgenic mice.
abstract: 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.
authors: Department of Neurology and Neurosurgery, Clinica Universitaria de Navarra, Universidad de Navarra, Pamplona, Navarre, Spain.
authors: María
authors: M
authors: Nieto
authors: Francisco J
authors: FJ
authors: Gil-Bea
authors: Esther
authors: E
authors: Dalfó
authors: Mar
authors: M
authors: Cuadrado
authors: Felipe
authors: F
authors: Cabodevilla
authors: Belén
authors: B
authors: Sánchez
authors: Silvia
authors: S
authors: Catena
authors: Teresa
authors: T
authors: Sesma
authors: Elena
authors: E
authors: Ribé
authors: Isidro
authors: I
authors: Ferrer
authors: María J
authors: MJ
authors: Ramírez
authors: Teresa
authors: T
authors: Gómez-Isla
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000367:Age Factors; D000409:Alanine / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007306:Insecticides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D011392:Proline / Q000235:genetics*; D012402:Rotenone / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D007306:Insecticides; D009498:Neurotoxins; D051844:alpha-Synuclein; D012402:Rotenone; D011392:Proline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000409:Alanine; D004298:Dopamine