DOI: 10.1523/jneurosci.5599-08.2009. <i>In Vivo</i>Evidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease

In VivoEvidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease

10.1523/jneurosci.5599-08.2009

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

N-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity is implicated as a proximate cause of neurodegeneration in Huntington Disease (HD). This hypothesis has not been tested rigorouslyin vivo. NMDAR–NR2B subunits are a major NR2 subunit expressed by striatal medium spiny neurons that degenerate in HD. To test the excitotoxic hypothesis, we crossed a well validated murine genetic model of HD (Hdh(CAG)150) with a transgenic line overexpressing NMDAR–NR2B subunits. In the resulting double-mutant line, we show exacerbation of selective striatal neuron degeneration. This is the first directin vivoevidence of NR2B–NMDAR-mediated excitotoxicity in the context of HD. Our results are consistent with previous suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.

Bibliography

Heng, M. Y., Detloff, P. J., Wang, P. L., Tsien, J. Z., & Albin, R. L. (2009). In VivoEvidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease. The Journal of Neuroscience, 29(10), 3200â3205.

Authors 5

Mary Y. Heng (first)
Peter J. Detloff (additional)
Phillip L. Wang (additional)
Joe Z. Tsien (additional)
Roger L. Albin (additional)

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Dates

Type	When
Created	16 years, 5 months ago (March 11, 2009, 5:34 p.m.)
Deposited	6 months, 3 weeks ago (Feb. 8, 2025, 3:14 a.m.)
Indexed	4 days, 17 hours ago (Aug. 26, 2025, 3:05 a.m.)
Issued	16 years, 5 months ago (March 11, 2009)
Published	16 years, 5 months ago (March 11, 2009)
Published Online	16 years, 5 months ago (March 11, 2009)
Published Print	16 years, 5 months ago (March 11, 2009)

Funders 0

None

BibTeX

@article{Heng_2009, title={In VivoEvidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease}, volume={29}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.5599-08.2009}, DOI={10.1523/jneurosci.5599-08.2009}, number={10}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Heng, Mary Y. and Detloff, Peter J. and Wang, Phillip L. and Tsien, Joe Z. and Albin, Roger L.}, year={2009}, month=mar, pages={3200–3205} }

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