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Cerebral Metabolic Effects of Monoamine Oxidase Inhibition in Normal and 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Acutely Treated Monkeys
Author(s) -
Palombo Ernesta,
Porrino Linda J.,
Crane Alison M.,
Bankiewicz Krzysztof S.,
Kopin Irwin J.,
Sokoloff Louis
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02062.x
Subject(s) - mptp , pargyline , pars compacta , substantia nigra , monoamine oxidase , dopaminergic , endocrinology , medicine , locus coeruleus , neurotoxin , chemistry , monoamine oxidase b , dopamine , biology , biochemistry , central nervous system , enzyme
The neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2‐deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP‐treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures.