Glutamate neurotoxicity in cortical cell culture. Choi, D W, Maulucci-Gedde, M, & Kriegstein, A R J Neurosci, 7(2):357–368, February, 1987. abstract bibtex 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.
@ARTICLE{Choi1987-kh,
title = "Glutamate neurotoxicity in cortical cell culture",
author = "Choi, D W and Maulucci-Gedde, M and Kriegstein, A R",
abstract = "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.",
journal = "J Neurosci",
volume = 7,
number = 2,
pages = "357--368",
month = feb,
year = 1987,
language = "en"
}
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