Linked Life Data

17433272

Source:http://linkedlifedata.com/resource/pubmed/id/17433272

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-5-14
pubmed:abstractText
Excessive glutamate (Glu) stimulation of the NMDA-R is a widely recognized trigger for Ca(2+)-mediated excitotoxicity. Primary neurons typically show a large increase in vulnerability to excitotoxicity with increasing days in vitro (DIV). This enhanced vulnerability has been associated with increased expression of the NR2B subunit or increased NMDA-R current, but the detailed age-courses of these variables in primary hippocampal neurons have not been compared in the same study. Further, it is not clear whether the NMDA-R is the only source of excess Ca(2+). Here, we used primary hippocampal neurons to examine the age dependence of the increase in excitotoxic vulnerability with changes in NMDA-R current, and subunit expression. We also tested whether L-type voltage-gated Ca(2+) channels (L-VGCCs) contribute to the enhanced vulnerability. The EC(50) for Glu toxicity decreased by approximately 10-fold between 8-9 and 14-15 DIV, changing little thereafter. Parallel experiments found that during the same period both amplitude and duration of NMDA-R current increased dramatically; this was associated with an increase in protein expression of the NR1 and NR2A subunits, but not of the NR2B subunit. Compared to MK-801, ifenprodil, a selective NR2B antagonist, was less effective in protecting older than younger neurons from Glu insult. Conversely, nimodipine, an L-VGCC antagonist, protected older but not younger neurons. Our results indicate that enhanced excitotoxic vulnerability with age in culture was associated with a substantial increase in NMDA-R current, concomitant increases in NR2A and NR1 but not NR2B subunit expression, and with apparent recruitment of L-VGCCs into the excitotoxic process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
1151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20-31
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17433272-Aging, pubmed-meshheading:17433272-Animals, pubmed-meshheading:17433272-Calcium, pubmed-meshheading:17433272-Calcium Channels, L-Type, pubmed-meshheading:17433272-Cell Survival, pubmed-meshheading:17433272-Cells, Cultured, pubmed-meshheading:17433272-Dizocilpine Maleate, pubmed-meshheading:17433272-Embryo, Mammalian, pubmed-meshheading:17433272-Female, pubmed-meshheading:17433272-Gene Expression, pubmed-meshheading:17433272-Glutamic Acid, pubmed-meshheading:17433272-Hippocampus, pubmed-meshheading:17433272-L-Lactate Dehydrogenase, pubmed-meshheading:17433272-Membrane Potentials, pubmed-meshheading:17433272-N-Methylaspartate, pubmed-meshheading:17433272-Neurons, pubmed-meshheading:17433272-Neuroprotective Agents, pubmed-meshheading:17433272-Patch-Clamp Techniques, pubmed-meshheading:17433272-Pregnancy, pubmed-meshheading:17433272-Rats, pubmed-meshheading:17433272-Rats, Sprague-Dawley, pubmed-meshheading:17433272-Receptors, N-Methyl-D-Aspartate
pubmed:year
2007
pubmed:articleTitle
Increased vulnerability of hippocampal neurons with age in culture: temporal association with increases in NMDA receptor current, NR2A subunit expression and recruitment of L-type calcium channels.
pubmed:affiliation
Department of Molecular and Biomedical Pharmacology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural