MPTP neurotoxicity to cerebellar Purkinje cells in mice.
The pyridine derivative 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is recognized as a crucial neurotoxin which destroys nigrostriatal dopamine cells, thereby inducing neurological signs relevant to idiopathic Parkinson's disease. In the present study, we have revealed MPTP neurotoxicity to cerebellar Purkinje cells in mice. Systemic MPTP injections to mice resulted in a substantial loss of Purkinje cells in a dose-dependent fashion. The MPTP-induced Purkinje cell loss occurred markedly in the crus I and II ansiform lobules and the paraflocculus. Such a neurotoxic effect was largely prevented by the monoamine oxidase B inhibitors pargyline and deprenyl, and the dopamine uptake inhibitors mazindol and benztropine.
Takada
M
M
Department of Anatomy and Cell Biology, University of Toronto, Ont., Canada.
Sugimoto
T
T
Hattori
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000818:Animals; D001590:Benztropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020267:MPTP Poisoning; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009498:Neurotoxins / Q000633:toxicity*; D010293:Pargyline / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000473:pathology*; D012642:Selegiline / Q000494:pharmacology
D009498:Neurotoxins; D001590:Benztropine; D012642:Selegiline; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008454:Mazindol