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Journal of Neuroscience, Vol 7, 357-368, Copyright © 1987 by Society for Neuroscience
Glutamate neurotoxicity in cortical cell culture
DW Choi, M Maulucci-Gedde and AR Kriegstein
The central neurotoxicity of the excitatory amino acid neurotransmitter
glutamate has been postulated to participate in the pathogenesis of the
neuronal cell loss associated with several neurological disease states, but
the complexity of the intact nervous system has impeded detailed analysis
of the phenomenon. In the present study, glutamate neurotoxicity was
studied with novel precision in dissociated cell cultures prepared from the
fetal mouse neocortex. Brief exposure to glutamate was found to produce
morphological changes in mature cortical neurons beginning as quickly as 90
sec after exposure, followed by widespread neuronal degeneration over the
next hours. Quantitative dose- toxicity study suggested an ED50 of 50-100
microM for a 5 min exposure to glutamate. Immature cortical neurons and
glia were not injured by such exposures to glutamate. Uptake processes
probably do not limit GNT in culture, as the uptake inhibitor
dihydrokainate did not potentiate GNT. Possibly reflecting the lack of
uptake limitation, glutamate was found to be actually more potent than
kainate as a neurotoxin in these cultures, a dramatic reversal of the in
vivo potency rank order. Some neurons regularly survived brief glutamate
exposure; these possibly glutamate-resistant neurons had electrophysiologic
properties, including chemosensitivity to glutamate, that were grossly
similar to those of the original population.
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