Neuropathological changes in the caudate nucleus elicited by MPTP and their prevention by monoamine oxidase inhibition.
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin producing parkinsonism, causes an obvious reduction in tyrosine hydroxylase (TH) activity in the caudate nucleus. This depletion of TH activity is due to degeneration of TH-positive punctate dopaminergic terminals. The disappearance of these terminals unmasks the presence of long branching, varicose preterminal fibers, which may be sprouting after degeneration of their terminal arborizations. Glial cells, normally sparse with delicate processes, undergo intense increase in number and a robust hypertrophy. All of these changes are prevented completely by administration of deprenyl, a monoamine oxidase inhibitor, before and after MPTP. These neuropathological effects are additional manifestations of the dopaminergic neurotoxicity induced by MPTP. The metabolism of MPTP, which is blocked by monoamine oxidase inhibition, is apparently necessary for the expression of toxicity in the brain by this neurotoxin.
Hess
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Department of Anatomy, Robert Wood Johnson Medical School, University of Medicine and Dentistry, Piscataway, NJ 08854.
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020267:MPTP Poisoning; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004791:Enzyme Inhibitors; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase