1710657

Chronic quinolinic acid lesions in rats closely resemble Huntington's disease.

Article date: 1991/6/1

PubMed ID: 1710657

Journal name: The Journal of neuroscience : the official journal of the Society for Neuroscience (ISSN: 0270-6474)

ABSTRACT

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.

This document is available from: http://directlinks.cc/files/muscimol/1710657.pdf

Author List: Beal M F, Ferrante R J, Swartz K J, Kowall N W

Publication Types: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Biogenic Amines; Glutamates; Neuropeptide Y; Quinolinic Acids; Ibotenic Acid; Substance P; Somatostatin; gamma-Aminobutyric Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; NADPH Dehydrogenase; Choline O-Acetyltransferase; Quinolinic Acid; Kainic Acid;

Mesh terms: Animals; Atrophy; Biogenic Amines/metabolism; Cerebral Cortex/drug effects; Choline O-Acetyltransferase/metabolism; Corpus Striatum/drug effects; Disease Models, Animal; Glutamates/metabolism; Huntington Disease/chemically induced; Ibotenic Acid/analogs & derivatives; Kainic Acid/toxicity; Male; Mesencephalon/drug effects; NADPH Dehydrogenase/metabolism; Neurons/drug effects; Neuropeptide Y/metabolism; Quinolinic Acid; Quinolinic Acids/toxicity; Rats; Rats, Inbred Strains; Reference Values; Somatostatin/metabolism; Substance P/metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid/metabolism;

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