Aging and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of dopaminergic neurons in the substantia nigra

摘要: Abstract This study assessed the influence of aging on substantia nigra degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive neuronal was found in older (8–12 months age) but not younger (6–8 weeks mice given MPTP. Older did have higher brain concentrations either MPTP or 1-methyl-4-phenylpyridinium (MPP + ), putative toxic metabolite MPTP, to account for greater toxicity. In fact, metabolized more rapidly than mice, probably because increase monoamine oxidase activity that occurs with aging. Striatal synaptosomes from accumulate [ 3 H]MPP mice. Thus, it is concluded neurodegenerative effect animals due levels uptake MPP , rather related a true sensitivity dopaminergic cells For comparative purposes, another neurotoxin, methamphetamine, tested. were sensitive young mature methamphetamine. finding indicates increased neurons selective. The link established here between and toxin which produces parkinsonism humans, provides mechanism an age-related disorder such as Parkinson's disease could be caused MPTP-like environment.