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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1997-2-18
|
| pubmed:abstractText |
Roles and mechanisms of N-methyl-D-aspartate (NMDA) receptors in glutamate neurotoxicity were investigated in cultures of NMDA receptor-deficient cortical neuronal cells. Mutant mice lacking a functional NMDA receptor were generated by gene targeting of the NR1 NMDA receptor subunit. Cortical neuronal cells prepared from wild-type NR1+/+, heterozygous NR1+/- and homozygous mutant NR1-/- mice at 15-17 days of gestation grew indistinguishably from each other. Brief exposures (5 min) of both NR1+/+ and NR1+/- neuronal cells to glutamate or NMDA, but not kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), resulted in widespread neuronal degeneration by the following day. In contrast, neither glutamate nor NMDA treatment caused neuronal degeneration in NR1-/- cells, indicating that NMDA receptors are responsible for rapidly triggered glutamate neurotoxicity. The above four compounds were all effective in inducing the death of NR1+/+ and NR1+/- neuronal cells after prolonged exposure (20-24 h). However, NMDA had no neurotoxic effects on NR1-/- cells, although the other three compounds wer neurotoxic with potencies comparable to those for NR1+/+ and NR1+/- cells. The AMPA and kainate receptors are thus sufficient for inducing slowly triggered glutamate neurotoxicity. Brief exposure of a mixed population of NR1+/+ and NR1-/- neuronal cells to NMDA selectively killed the NMDA receptor-expressing cells without any appreciable effects on neighbouring NMDA receptor-deficient cells. This finding further supports a direct and indispensable role for NMDA receptors in NMDA-evoked neuronal cell death.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0953-816X
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
69-78
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8713451-Animals,
pubmed-meshheading:8713451-Cell Survival,
pubmed-meshheading:8713451-Cells, Cultured,
pubmed-meshheading:8713451-Cerebral Cortex,
pubmed-meshheading:8713451-Chimera,
pubmed-meshheading:8713451-Female,
pubmed-meshheading:8713451-Glutamic Acid,
pubmed-meshheading:8713451-Membrane Potentials,
pubmed-meshheading:8713451-Mice,
pubmed-meshheading:8713451-Mice, Inbred BALB C,
pubmed-meshheading:8713451-Mice, Inbred ICR,
pubmed-meshheading:8713451-Mice, Neurologic Mutants,
pubmed-meshheading:8713451-N-Methylaspartate,
pubmed-meshheading:8713451-Neurons,
pubmed-meshheading:8713451-Neurotoxins,
pubmed-meshheading:8713451-Receptors, AMPA,
pubmed-meshheading:8713451-Receptors, Kainic Acid,
pubmed-meshheading:8713451-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:8713451-Stem Cells,
pubmed-meshheading:8713451-Transfection
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Characterization of excitatory amino acid neurotoxicity in N-methyl-D-aspartate receptor-deficient mouse cortical neuronal cells.
|
| pubmed:affiliation |
Institute for Immunology, Kyoto University Faculty of Medicine, Japan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|