Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/105847
- author
- Zeron, Melinda M ; Hansson, Oskar LU ; Chen, Nansheng ; Wellington, Cheryl L ; Leavitt, Blair R ; Brundin, Patrik LU ; Hayden, Michael R and Raymond, Lynn A
- organization
- publishing date
- 2002
- 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
- 2022-03-20 19:01:00
@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}}, }