Article date: 1991/12/11
PubMed ID: 1665055
Journal name: Annals of neurology (ISSN: 0364-5134)
Huntington's disease is a dominantly inherited, progressive neurodegenerative disorder causing marked pathology in the basal ganglia. The pathophysiology of the selective neuronal death is as yet unknown, but evidence suggests that the neurotoxicity may result from endogenous substances acting at excitatory amino acid receptors. Previous data have shown a selective decrease in binding to one class of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor in the putamen of Huntington's disease. The present study was undertaken to determine the relative density of binding to all of the currently defined subpopulations of excitatory amino acid receptors in the caudate nuclei and frontal cortex of patients with Huntington's disease and of control subjects, using quantitative in vitro autoradiography. NMDA, MK-801, glycine, kainate, and alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor binding were all decreased to a similar extent (50-60%). Binding to the metabotropic quisqualate receptor and to the non-NMDA, nonkainate, nonquisqualate (NNKQ) site was decreased nonsignificantly by 31% and 26%, respectively. Autoradiograms of NMDA, MK-801, AMPA, kainate, metabotropic, and NNKQ receptors in caudates revealed an inhomogeneous pattern of binding that is different from the binding pattern seen in control caudates. Binding to all receptor subtypes was the same in the frontal cortex from Huntington's disease patients and control subjects. The data suggest that no single excitatory amino acid receptor is selectively decreased in the caudate of Huntington's disease.
Author List: Dure L S, Young A B, Penney J B
Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Receptors, AMPA; Receptors, Glutamate; Receptors, Glycine; Receptors, Kainic Acid; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Receptors, Phencyclidine; metabotropic quisqualate receptor; Ibotenic Acid; N-Methylaspartate; Dizocilpine Maleate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Phencyclidine; Kainic Acid; Glycine;
Mesh terms: Adolescent; Adult; Age Factors; Aged; Binding, Competitive; Caudate Nucleus/chemistry; Cell Death; Child; Dizocilpine Maleate/metabolism; Frontal Lobe/chemistry; Glycine/metabolism; Humans; Huntington Disease/metabolism; Ibotenic Acid/analogs & derivatives; Kainic Acid/metabolism; Middle Aged; N-Methylaspartate/metabolism; Phencyclidine/metabolism; Receptors, AMPA; Receptors, Glutamate; Receptors, Glycine; Receptors, Kainic Acid; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate/analysis; Receptors, Neurotransmitter/analysis; Receptors, Phencyclidine; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;