Excitatory amino acid neurotoxicity in cultured retinal neurons: Involvement of N‐methyl‐D‐Aspartate (NMDA) and Non‐NMDA receptors and effect of ganglioside GM1

Excitatory amino acid neurotoxicity in cultured retinal neurons: Involvement of... Cultures of chicken day 8 embryo retinal cells, essentially free of contaminating non‐neuronal elements, were used to examine the neurotoxicity of various excitatory amino acid transmitter receptor agonists. At 7 days in vitro, N‐methyl‐D‐aspartate (NMDA), following 24 hr exposure to 0.1‐1.0 mM, destroyed 60‐70% of the multipolar neurons, but apparently spared photoreceptors. The cytotoxic effect of NMDA was prevented by extracellular Mg2+ or phencyclidine, suggesting a role for the NMDA ion channel; competitive NMDA antagonists were also neuroprotective. The mixed excitatory amino acid receptor agonist glutamate (0.1‐1.0 mM) was also neurotoxic (∼70% loss of multipolar neurons) and strongly blocked by NMDA (but weakly by non‐NMDA) antagonists and Mg2+, indicating a major action at NMDA receptors. As with NMDA, glutamate did not appear to affect photoreceptors. The neurotoxic action of kainate against multipolar retinal neurons, as reported by others, was confirmed here. Kainate neuronal injury was sensitive to the quinoxalinedione non‐NMDA antagonists 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) and 6‐cyanoquinoxaline‐2,3‐dione (CNQX), but not to Mg2+ or phencyclidine. Ibotenate and quisqualate, even at millimolar concentrations, were not neurotoxic. The monosialoganglioside GM1 was also effective in reducing NMDA and non‐NMDA agonist neurotoxicity to retinal neurons. Maximal ganglioside benefit required 1‐2 hr of pre‐treatment with 100‐200 μM GM1.The percentage of multipolar neurons remaining after the neurotoxin insult approximately doubled with GM1 treatment. Gangliosides may thus have a therapeutic potential in excitatory amino acid‐initiated neuropathologies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

Excitatory amino acid neurotoxicity in cultured retinal neurons: Involvement of N‐methyl‐D‐Aspartate (NMDA) and Non‐NMDA receptors and effect of ganglioside GM1

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Publisher
Wiley
Copyright
Copyright © 1990 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/jnr.490270210
Publisher site
See Article on Publisher Site

Abstract

Cultures of chicken day 8 embryo retinal cells, essentially free of contaminating non‐neuronal elements, were used to examine the neurotoxicity of various excitatory amino acid transmitter receptor agonists. At 7 days in vitro, N‐methyl‐D‐aspartate (NMDA), following 24 hr exposure to 0.1‐1.0 mM, destroyed 60‐70% of the multipolar neurons, but apparently spared photoreceptors. The cytotoxic effect of NMDA was prevented by extracellular Mg2+ or phencyclidine, suggesting a role for the NMDA ion channel; competitive NMDA antagonists were also neuroprotective. The mixed excitatory amino acid receptor agonist glutamate (0.1‐1.0 mM) was also neurotoxic (∼70% loss of multipolar neurons) and strongly blocked by NMDA (but weakly by non‐NMDA) antagonists and Mg2+, indicating a major action at NMDA receptors. As with NMDA, glutamate did not appear to affect photoreceptors. The neurotoxic action of kainate against multipolar retinal neurons, as reported by others, was confirmed here. Kainate neuronal injury was sensitive to the quinoxalinedione non‐NMDA antagonists 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) and 6‐cyanoquinoxaline‐2,3‐dione (CNQX), but not to Mg2+ or phencyclidine. Ibotenate and quisqualate, even at millimolar concentrations, were not neurotoxic. The monosialoganglioside GM1 was also effective in reducing NMDA and non‐NMDA agonist neurotoxicity to retinal neurons. Maximal ganglioside benefit required 1‐2 hr of pre‐treatment with 100‐200 μM GM1.The percentage of multipolar neurons remaining after the neurotoxin insult approximately doubled with GM1 treatment. Gangliosides may thus have a therapeutic potential in excitatory amino acid‐initiated neuropathologies.

Journal

Journal of Neuroscience ResearchWiley

Published: Oct 1, 1990

References

  • Glutamate neurotoxicity in cortical cell culture
    Choi, Choi; Maulucci‐Gedde, Maulucci‐Gedde; Kriegsten, Kriegsten
  • Glutamate: a neurotransmitter in mammalian brain
    Fonnum, Fonnum
  • GM1 ganglioside protects nucleus basalis from excitotoxin damage: reduced cortical cholinergic losses and animal mortality
    Mahadik, Mahadik; Vilim, Vilim; Korenovsky, Korenovsky; Karpiak, Karpiak
  • Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous, system
    Olney, Olney; Ho, Ho; Rhee, Rhee
  • Glutamate and the pathophysiology of hypoxic‐ischemic brain damage
    Rothman, Rothman; Olney, Olney
  • Expression of transfected genes by differentiated, postmitotic neurons and photoreceptors in primary cell cultures
    Werner, Werner; Madreperla, Madreperla; Lieberman, Lieberman; Adler, Adler
  • Excitatory amino acid‐induced toxicity in chick retina: amino acid release, histology, and effects of chloride channel blockers
    Zeevalk, Zeevalk; Hyndman, Hyndman; Nicklas, Nicklas

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