Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 19 August 1988:
Vol. 241. no. 4868, pp. 981 - 983
DOI: 10.1126/science.2841762

Articles

Science, Vol 241, Issue 4868, 981-983
Copyright © 1988 by American Association for the Advancement of Science


articles

NMDA receptor losses in putamen from patients with Huntington's disease

AB Young, JT Greenamyre, Z Hollingsworth, R Albin, C D'Amato, I Shoulson, and JB Penney

Department of Neurology, University of Michigan, Ann Arbor 48109.

N-Methyl-D-aspartate (NMDA), phencyclidine (PCP), and quisqualate receptor binding were compared to benzodiazepine, gamma-aminobutyric acid (GABA), and muscarinic cholinergic receptor binding in the putamen and cerebral cortex of individuals with Huntington's disease (HD). NMDA receptor binding was reduced by 93 percent in putamen from HD brains compared to binding in normal brains. Quisqualate and PCP receptor binding were reduced by 67 percent, and the binding to other receptors was reduced by 55 percent or less. Binding to these receptors in the cerebral cortex was unchanged in HD brains. The results support the hypothesis that NMDA receptor-mediated neurotoxicity plays a role in the pathophysiology of Huntington's disease.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Interaction of Postsynaptic Density Protein-95 with NMDA Receptors Influences Excitotoxicity in the Yeast Artificial Chromosome Mouse Model of Huntington's Disease.
J. Fan, C. M. Cowan, L. Y. J. Zhang, M. R. Hayden, and L. A. Raymond (2009)
J. Neurosci. 29, 10928-10938
   Abstract »    Full Text »    PDF »
Prevention of depressive behaviour in the YAC128 mouse model of Huntington disease by mutation at residue 586 of huntingtin.
M. A. Pouladi, R. K. Graham, J. M. Karasinska, Y. Xie, R. D. Santos, A. Petersen, and M. R. Hayden (2009)
Brain 132, 919-932
   Abstract »    Full Text »    PDF »
Polyglutamine-Modulated Striatal Calpain Activity in YAC Transgenic Huntington Disease Mouse Model: Impact on NMDA Receptor Function and Toxicity.
C. M. Cowan, M. M. Y. Fan, J. Fan, J. Shehadeh, L. Y. J. Zhang, R. K. Graham, M. R. Hayden, and L. A. Raymond (2008)
J. Neurosci. 28, 12725-12735
   Abstract »    Full Text »    PDF »
Altered NMDA Receptor Trafficking in a Yeast Artificial Chromosome Transgenic Mouse Model of Huntington's Disease.
M. M. Y. Fan, H. B. Fernandes, L. Y. J. Zhang, M. R. Hayden, and L. A. Raymond (2007)
J. Neurosci. 27, 3768-3779
   Abstract »    Full Text »    PDF »
Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds.
J M Andresen, J Gayan, S S Cherny, D Brocklebank, G Alkorta-Aranburu, E A Addis, The US-Venezuela Collaborative Research Group, L R Cardon, D E Housman, and N S Wexler (2007)
J. Med. Genet. 44, 44-50
   Abstract »    Full Text »    PDF »
Expression of Polyglutamine-expanded Huntingtin Induces Tyrosine Phosphorylation of N-Methyl-D-aspartate Receptors.
C. Song, Y. Zhang, C. G. Parsons, and Y. F. Liu (2003)
J. Biol. Chem. 278, 33364-33369
   Abstract »    Full Text »    PDF »
Identification and Expression of a cDNA Encoding Human alpha -Amino-beta -carboxymuconate-epsilon -semialdehyde Decarboxylase (ACMSD). A KEY ENZYME FOR THE TRYPTOPHAN-NIACINE PATHWAY AND "QUINOLINATE HYPOTHESIS".
S.-I. Fukuoka, K. Ishiguro, K. Yanagihara, A. Tanabe, Y. Egashira, H. Sanada, and K. Shibata (2002)
J. Biol. Chem. 277, 35162-35167
   Abstract »    Full Text »    PDF »
The influence of excitotoxic basal ganglia lesions on motor performance in the common marmoset.
A. L. Kendall, F. David, G. Rayment, E. M. Torres, L. E. Annett, and S. B. Dunnett (2000)
Brain 123, 1442-1458
   Abstract »    Full Text »    PDF »
Geometry and Charge Determine Pharmacological Effects of Steroids on N-Methyl-D-aspartate Receptor-Induced Ca2+ Accumulation and Cell Death.
C. E. Weaver, M. B. Land, R. H. Purdy, K. G. Richards, T. T. Gibbs, and D. H. Farb (2000)
J. Pharmacol. Exp. Ther. 293, 747-754
   Abstract »    Full Text »
Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity.
O. Hansson, A. Petersen, M. Leist, P. Nicotera, R. F. Castilho, and P. Brundin (1999)
PNAS 96, 8727-8732
   Abstract »    Full Text »    PDF »
Cellular Localization of Huntingtin in Striatal and Cortical Neurons in Rats: Lack of Correlation with Neuronal Vulnerability in Huntington's Disease.
F. R. Fusco, Q. Chen, W. J. Lamoreaux, G. Figueredo-Cardenas, Y. Jiao, J. A. Coffman, D. J. Surmeier, M. G. Honig, L. R. Carlock, and A. Reiner (1999)
J. Neurosci. 19, 1189-1202
   Abstract »    Full Text »    PDF »
Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications.
W. Danysz and C. G. Parsons (1998)
Pharmacol. Rev. 50, 597-664
   Abstract »    Full Text »    PDF »
Cellular, Subcellular, and Subsynaptic Distribution of AMPA-Type Glutamate Receptor Subunits in the Neostriatum of the Rat.
V. Bernard, P. Somogyi, and J. P. Bolam (1997)
J. Neurosci. 17, 819-833
   Abstract »    Full Text »    PDF »
Abnormal Excitatory Neurotransmitter Metabolism in Schizophrenic Brains.
G. Tsai, L. A. Passani, B. S. Slusher, R. Carter, L. Baer, J. E. Kleinman, and J. T. Coyle (1995)
Arch Gen Psychiatry 52, 829-836
   Abstract »    PDF »
Neurotrophic Factor Protection against Excitotoxic Neuronal Death.
S. B. Tatter, W. R. Galpern, and O. Isacson (1995)
Neuroscientist 1, 286-297
   Abstract »    PDF »
N-Methyl-d-Aspartate Antagonists in the Treatment of Parkinson's Disease.
J. T. Greenamyre and C. F. O'Brien (1991)
Arch Neurol 48, 977-981
   Abstract »    PDF »
Molecular cloning and functional expression of glutamate receptor subunit genes.
J Boulter, M Hollmann, A O'Shea-Greenfield, M Hartley, E Deneris, C Maron, and S Heinemann (1990)
Science 249, 1033-1037
   Abstract »    PDF »
The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity.
J. Weiss, D. Hartley, J Koh, and D. Choi (1990)
Science 247, 1474-1477
   Abstract »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)