Title

Age-related decreases in GTP-cyclohydrolase-I immunoreactive neurons in the monkey and human substantia nigra

Document Type

Article

Abstract

Guanosine triphosphate cyclohydrolase I (GTPCHI) is a critical enzyme in catecholamine function and is rate limiting for the synthesis of the catecholamine co-factor tetrahydrobiopterin. The present study assessed the distribution of GTPCHI immunoreactivity (-ir) within the monkey and human ventral midbrain and determined whether its expression is altered as a function of age. Light and confocal microscopic analyses revealed that young monkeys and humans displayed GTPCHI-ir within melanin-containing and tyrosine-hydroxylase-ir neurons in primate substantia nigra. Stereological counts revealed that there was a 67.4% reduction in GTPCHI-ir neuronal number, a 63.5% reduction in GTPCHI-ir neuronal density, and a 37.6% reduction in neuronal volume in aged monkeys relative to young cohorts. Similar age-related changes were seen in humans, in whom there were significant reductions in the number of GTPCHI-ir nigral neurons in middle age (58.4%) and aged (81.5%) cases relative to young cohorts. The density of GTPCHI-ir neurons within the nigra was similarly reduced in middle-aged (63.0%) and aged (81.8%) cases. In contrast to monkeys, aged humans did not display shrinkage in the volume of GTPCHI-ir nigral neurons. The presence of numerous melanin-positive, but GTPCHI-ir immunonegative, neurons in the aged monkey and human nigra indicates that these decreases represent an age-related phenotypic downregulation of this enzyme and not a loss of neurons per se. These data indicate that there is a dramatic decrease in GTPCHI-ir in nonhuman primates and humans as a function of age and that loss of this enzyme may be partly responsible for the age-related decrease in dopaminergic tone within nigrostriatal systems. (C) 2000 Wiley-Liss, Inc.

Keywords

Aging, GTPCHI, Human, Monkeys, Parkinson's disease, Substantia nigra

Publication Date

1-1-2000

Publication Title

Journal of Comparative Neurology

ISSN

00219967

Volume

426

Issue

4

First Page

534

Last Page

548

PubMed ID

11027397

Digital Object Identifier (DOI)

10.1002/1096-9861(20001030)426:4<534::AID-CNE3>3.0.CO;2-G

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