A leading hypothesis of the cause of neuronal death in Huntington’s disease (HD) is excitotoxicity, in which subpopulations of striatal neurons are hypersensitive to glutamate release due to changes in postsynaptic N-methyl-D-aspartate receptors (NMDARs). In the present study we used RT-PCR methods on single cells and tissue to compare the expression of NMDAR subunits, NR1, NR2A and NR2B, in the striatum of R6/2 transgenic mice with their wild-type (WT) littermates at three different age groups corresponding to different symptomatic milestones (19–25 days showing no overt evidence of abnormal behavior, 38–45 days at the onset of the overt phenotype and 78–90 days displaying the full behavioral phenotype). Single-cell RT-PCR studies also examined neurons for the expression of substance P and enkephalin to define different subpopulations of medium-sized projection neurons of the striatum. The results showed a significant decrease in the percentage of cells expressing NR2A at all ages examined. The decrease in expression was not associated with any significant change in expression of NR1 or NR2B. Cells that did not express NR2A contained both enkephalin and substance P, but proportionately more cells containing enkephalin displayed decreases in NR2A. Semi-quantitative RT-PCR studies on striatal tissue in the oldest age group confirmed the significant decrease in NR2A and also showed a decrease in NR2B. These results support the hypothesis that changes in the composition of postsynaptic NMDARs occur in the R6/2 model of HD and this effect occurs early in the expression of the phenotype.
© 2006 S. Karger AG, Basel
- Huntington’s disease
- R6/2 mouse model
- N-methyl-D-aspartate receptors
- Receptor subunit RNA
- Single-cell RT-PCR
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Michael S. Levine, PhD
Mental Retardation Research Center
The David Geffen School of Medicine, 760 Westwood Plaza NPI 58-258
University of California, Los Angeles, CA 90095 (USA)
Tel. +1 310 825 7595, Fax +1 310 206 5060, E-Mail firstname.lastname@example.org
Received: September 19, 2005
Accepted: October 22, 2005
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 0, Number of References : 41
Vol. 28, No. 3, Year 2006 (Cover Date: May 2006)
Journal Editor: Campagnoni, A.T. (Los Angeles, Calif.)
ISSN: 0378–5866 (print), 1421–9859 (Online)
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