Linked Life Data

2481321

Source:http://linkedlifedata.com/resource/pubmed/id/2481321

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1990-1-31
pubmed:abstractText
Using rat cerebellar granule cells in primary culture as our model system, we have shown that excitatory amino acids (EAAs) become neurotoxic via the NMDA (N-methyl-D-aspartate) receptor when neuronal energy levels are compromised. Omission of glucose, exclusion of oxygen, or inclusion of inhibitors of oxidative phosphorylation or of Na+/K+-ATPases enables NMDA receptor agonists to express their neurotoxic potential. Both competitive and noncompetitive NMDA receptor antagonists are potent blockers of EAA neurotoxicity, with MK-801 fully effective at 20 nM. We interpret these results as indicating that glucose metabolism, ATP production, and functioning ion pumps are necessary to generate a resting potential sufficient to maintain the voltage-dependent Mg++ block of the NMDA receptor channel; relief of the block enables EAAs to act persistently at the NMDA receptor causing an excessive ion influx which leads to neuronal death by a mechanism not yet understood. These findings are discussed in the context of the potential role for NMDA receptor-mediated neurotoxicity in Alzheimer's disease and related disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0361-7742
pubmed:author
pubmed:issnType
Print
pubmed:volume
317
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-56
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Energy-related neurotoxicity at the NMDA receptor: a possible role in Alzheimer's disease and related disorders.
pubmed:affiliation
Laboratory of Molecular Biology NINDS, NIH, Bethesda, MD 20892.
pubmed:publicationType
Journal Article