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Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors.
J Neurosci Res. 2005 Jul 15; 81(2):199-207.JN

Abstract

Extracellular glutamate is kept below a toxic level by glial and neuronal glutamate transporters. Here we show that the transportable glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (t-PDC) induced cell death in mature, but not in immature, hippocampal neuron-enriched cultures. The cell death produced by a 24-hr treatment with t-PDC was dose-dependent and reached 85% of the cell population at a 250 microM concentration at 23 days in vitro (DIV). Immunocytochemistry experiments showed that, under these experimental conditions, t-PDC killed not only neurons as expected but also glial cells. The N-methyl-D-aspartate (NMDA) antagonist D-2-aminophosphonovalerate (D-APV; 250 microM) only partially reversed this toxicity, completely protecting the neuronal cell population but not the glial population. The antioxidant compounds alpha-tocopherol or Trolox, used at concentrations that reverse the oxidative stress-induced toxicity, did not block the gliotoxicity specifically produced by t-PDC in the presence of D-APV. The nontransportable glutamate uptake inhibitor DL-threo-beta-benzyloxyaspartate (TBOA) elicited cell death only in mature, but not in immature, hippocampal cultures. The TBOA toxic effect was dose dependent and reached a plateau at 100 microM in 23-DIV cultures. About 50% of the cell population died. TBOA affected essentially the neuronal population. D-APV (250 microM) completely reversed this toxicity. It is concluded that nontransportable glutamate uptake inhibitors are neurotoxic via overactivation of NMDA receptors, whereas transportable glutamate uptake inhibitors induce both an NMDA-dependent neurotoxicity and an NMDA- and oxidative stress-independent gliotoxicity, but only in mature hippocampal cultures.

Authors+Show Affiliations

CNRS FRE 2693, Laboratoire de Plasticité Cérébrale, Université Montpellier II CC90, Montpellier, France. jguirama@univ-montp2.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15931685

Citation

Guiramand, Janique, et al. "Gliotoxicity in Hippocampal Cultures Is Induced By Transportable, but Not By Nontransportable, Glutamate Uptake Inhibitors." Journal of Neuroscience Research, vol. 81, no. 2, 2005, pp. 199-207.
Guiramand J, Martin A, de Jesus Ferreira MC, et al. Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors. J Neurosci Res. 2005;81(2):199-207.
Guiramand, J., Martin, A., de Jesus Ferreira, M. C., Cohen-Solal, C., Vignes, M., & Récasens, M. (2005). Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors. Journal of Neuroscience Research, 81(2), 199-207.
Guiramand J, et al. Gliotoxicity in Hippocampal Cultures Is Induced By Transportable, but Not By Nontransportable, Glutamate Uptake Inhibitors. J Neurosci Res. 2005 Jul 15;81(2):199-207. PubMed PMID: 15931685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors. AU - Guiramand,Janique, AU - Martin,Alexandra, AU - de Jesus Ferreira,Marie-Celeste, AU - Cohen-Solal,Catherine, AU - Vignes,Michel, AU - Récasens,Max, PY - 2005/6/3/pubmed PY - 2005/11/4/medline PY - 2005/6/3/entrez SP - 199 EP - 207 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 81 IS - 2 N2 - Extracellular glutamate is kept below a toxic level by glial and neuronal glutamate transporters. Here we show that the transportable glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (t-PDC) induced cell death in mature, but not in immature, hippocampal neuron-enriched cultures. The cell death produced by a 24-hr treatment with t-PDC was dose-dependent and reached 85% of the cell population at a 250 microM concentration at 23 days in vitro (DIV). Immunocytochemistry experiments showed that, under these experimental conditions, t-PDC killed not only neurons as expected but also glial cells. The N-methyl-D-aspartate (NMDA) antagonist D-2-aminophosphonovalerate (D-APV; 250 microM) only partially reversed this toxicity, completely protecting the neuronal cell population but not the glial population. The antioxidant compounds alpha-tocopherol or Trolox, used at concentrations that reverse the oxidative stress-induced toxicity, did not block the gliotoxicity specifically produced by t-PDC in the presence of D-APV. The nontransportable glutamate uptake inhibitor DL-threo-beta-benzyloxyaspartate (TBOA) elicited cell death only in mature, but not in immature, hippocampal cultures. The TBOA toxic effect was dose dependent and reached a plateau at 100 microM in 23-DIV cultures. About 50% of the cell population died. TBOA affected essentially the neuronal population. D-APV (250 microM) completely reversed this toxicity. It is concluded that nontransportable glutamate uptake inhibitors are neurotoxic via overactivation of NMDA receptors, whereas transportable glutamate uptake inhibitors induce both an NMDA-dependent neurotoxicity and an NMDA- and oxidative stress-independent gliotoxicity, but only in mature hippocampal cultures. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15931685/Gliotoxicity_in_hippocampal_cultures_is_induced_by_transportable_but_not_by_nontransportable_glutamate_uptake_inhibitors_ L2 - https://doi.org/10.1002/jnr.20557 DB - PRIME DP - Unbound Medicine ER -