Glutamate Triggers Cell Death Specifically in Mature Central Neurons through a Necrotic Process

Glutamate Triggers Cell Death Specifically in Mature Central Neurons through a Necrotic Process Whereas immature neurons have been shown to be sensitive to hypoxia and to develop apoptosis, the role of glutamate in neuronal injury is more controversial. Effects of a 6-h exposure to glutamate or its analogues (100 μM) were studied over a period of 72 h in cultured central neurons at two maturational stages, i.e., after 6 and 13 days in vitro. Glutamate was without toxic effects in 6-day-old neurons which became vulnerable to the excitatory amino acid when they were coexposed to 30 nM staurosporine, a protein kinase C inhibitor. In 13-day-old neurons, glutamate and derivatives led to cell death and altered functional activity of surviving neurons over the next 72 h, the greatest injury being observed with glutamate and NMDA. At this developmental stage, persistent inhibition of protein synthesis induced by glutamate, as well as lack of beneficial effect from cycloheximide, argues against programmed neuronal death. Accordingly, quantitative cell nuclear analysis using a fluorescent dye revealed that the effects of glutamate reflect necrosis but not apoptosis. Furthermore, the inability of immature neurons to inhibit protein kinase C may account for their higher resistance to excitotoxicity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Genetics and Metabolism Elsevier

Glutamate Triggers Cell Death Specifically in Mature Central Neurons through a Necrotic Process

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Publisher
Elsevier
Copyright
Copyright © 1998 Academic Press
ISSN
1096-7192
eISSN
1096-7206
DOI
10.1006/mgme.1997.2644
Publisher site
See Article on Publisher Site

Abstract

Whereas immature neurons have been shown to be sensitive to hypoxia and to develop apoptosis, the role of glutamate in neuronal injury is more controversial. Effects of a 6-h exposure to glutamate or its analogues (100 μM) were studied over a period of 72 h in cultured central neurons at two maturational stages, i.e., after 6 and 13 days in vitro. Glutamate was without toxic effects in 6-day-old neurons which became vulnerable to the excitatory amino acid when they were coexposed to 30 nM staurosporine, a protein kinase C inhibitor. In 13-day-old neurons, glutamate and derivatives led to cell death and altered functional activity of surviving neurons over the next 72 h, the greatest injury being observed with glutamate and NMDA. At this developmental stage, persistent inhibition of protein synthesis induced by glutamate, as well as lack of beneficial effect from cycloheximide, argues against programmed neuronal death. Accordingly, quantitative cell nuclear analysis using a fluorescent dye revealed that the effects of glutamate reflect necrosis but not apoptosis. Furthermore, the inability of immature neurons to inhibit protein kinase C may account for their higher resistance to excitotoxicity.

Journal

Molecular Genetics and MetabolismElsevier

Published: Feb 1, 1998

References

  • Glutamate: Its role in learning, memory, and the aging brain
    McEntee, WJ; Crook, TH
  • Glutamate-mediated injury in focal cerebral ischemia: The excitotoxin hypothesis revised
    Hossmann, KA
  • Changes in the activity of protein kinase C and the differential subcellular redistribution of its isozymes in the rat striatum during and following transient forebrain ischemia
    Wieloch, T; Cardell, M; Bingren, H; Zivin, J; Saitoh, T

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