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Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease.

Zeron, Melinda M ; Hansson, Oskar LU orcid ; Chen, Nansheng ; Wellington, Cheryl L ; Leavitt, Blair R ; Brundin, Patrik LU ; Hayden, Michael R and Raymond, Lynn A (2002) In Neuron 33(6). p.849-860
Abstract
Previous work suggests N-methyl-D-aspartate receptor (NMDAR) activation may be involved in degeneration of medium-sized spiny striatal neurons in Huntington's disease (HD). Here we show that these neurons are more vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice. Excitotoxic death of these neurons was increased after intrastriatal injection of quinolinate in vivo, and after NMDA but not AMPA exposure in culture. NMDA-induced cell death was abolished by an NR2B subtype-specific antagonist. In contrast, NMDAR-mediated death of cerebellar granule neurons was not enhanced, consistent with cell-type and NMDAR subtype specificity. Moreover,... (More)
Previous work suggests N-methyl-D-aspartate receptor (NMDAR) activation may be involved in degeneration of medium-sized spiny striatal neurons in Huntington's disease (HD). Here we show that these neurons are more vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice. Excitotoxic death of these neurons was increased after intrastriatal injection of quinolinate in vivo, and after NMDA but not AMPA exposure in culture. NMDA-induced cell death was abolished by an NR2B subtype-specific antagonist. In contrast, NMDAR-mediated death of cerebellar granule neurons was not enhanced, consistent with cell-type and NMDAR subtype specificity. Moreover, increased NMDA-evoked current amplitude and caspase-3 activity were observed in transgenic striatal neurons. Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Patch-Clamp Techniques, Nerve Tissue Proteins, Huntington Disease, Cell Death, N-Methylaspartate, Nuclear Proteins
in
Neuron
volume
33
issue
6
pages
849 - 860
publisher
Cell Press
external identifiers
  • wos:000174389600004
  • pmid:11906693
  • scopus:0037075624
ISSN
0896-6273
DOI
10.1016/S0896-6273(02)00615-3
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Psychiatry/Primary Care/Public Health (013240500), Neuronal Survival (013212041)
id
09c7c4ff-836e-45d6-8acc-b7b4feac4a78 (old id 105847)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11906693&dopt=Abstract
date added to LUP
2016-04-01 11:47:55
date last changed
2025-10-14 09:14:13
@article{09c7c4ff-836e-45d6-8acc-b7b4feac4a78,
  abstract     = {{Previous work suggests N-methyl-D-aspartate receptor (NMDAR) activation may be involved in degeneration of medium-sized spiny striatal neurons in Huntington's disease (HD). Here we show that these neurons are more vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice. Excitotoxic death of these neurons was increased after intrastriatal injection of quinolinate in vivo, and after NMDA but not AMPA exposure in culture. NMDA-induced cell death was abolished by an NR2B subtype-specific antagonist. In contrast, NMDAR-mediated death of cerebellar granule neurons was not enhanced, consistent with cell-type and NMDAR subtype specificity. Moreover, increased NMDA-evoked current amplitude and caspase-3 activity were observed in transgenic striatal neurons. Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD.}},
  author       = {{Zeron, Melinda M and Hansson, Oskar and Chen, Nansheng and Wellington, Cheryl L and Leavitt, Blair R and Brundin, Patrik and Hayden, Michael R and Raymond, Lynn A}},
  issn         = {{0896-6273}},
  keywords     = {{Patch-Clamp Techniques; Nerve Tissue Proteins; Huntington Disease; Cell Death; N-Methylaspartate; Nuclear Proteins}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{849--860}},
  publisher    = {{Cell Press}},
  series       = {{Neuron}},
  title        = {{Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease.}},
  url          = {{http://dx.doi.org/10.1016/S0896-6273(02)00615-3}},
  doi          = {{10.1016/S0896-6273(02)00615-3}},
  volume       = {{33}},
  year         = {{2002}},
}