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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