Kainate-induced status epilepticus alters glutamate and GABA(A) receptor gene expression in adult rat hippocampus: An in situ hybridization study

L. K. Friedman, D. E. Pellegrini-Giampietro, E. F. Sperber, M. V.L. Bennett, S. L. Moshe, R. S. Zukin

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Abstract

In adult rats, intraperitoneal administration of kainic acid, a glutamic acid analog and potent neurotoxin, induces persistent seizure activity that results in electrographic alterations and neuropathology that closely resemble human temporal lobe epilepsy. We used in situ hybridization to identify regions of altered glutamate and GABA(A) receptor gene expression following kainate-induced status epilepticus. In the CA3/CA4 area, the hippocampal region most vulnerable to neurodegeneration after kainate acid treatment, expression of GluR2 (the AMPA/kainate receptor subunit that limits Ca2+ permeability) and GluR3 was decreased markedly at 12 and 24 hr, times preceding neurodegeneration. These findings raise the possibility that increased formation of Ca2+-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABA(A) α1 subunit was also reduced, indicating a possible decrease in inhibitory transmission, which would also enhance excitotoxicity. GluR1 and NR1 expression was not significantly changed. In the dentate gyrus, a region resistant to neurodegeneration, concomitant increases in GluR2 and GluR3 expression were observed; GluR1, NR1, and GABA(A) α1 mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABA(A) α1 expression represented changes in mRNA content per neuron and were specific to pyramidal cells of the CA3/CA4 area and to granule cells of the dentate gyrus. These findings indicate that kainate seizures modify hippocampal glutamate and GABA(A) receptor expression in a cell-specific manner. Timing of the changes in glutamate and GABA(A) receptor mRNAs indicates that these changes may play a causal role in hippocampal neuronal cell loss following kainate-induced seizures.

Original languageEnglish (US)
Pages (from-to)2697-2707
Number of pages11
JournalJournal of Neuroscience
Volume14
Issue number5 I
StatePublished - Jan 1 1994

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Keywords

  • AMPA receptors
  • NMDA receptors
  • epilepsy
  • kainate receptors
  • receptor mRNAs
  • seizures

ASJC Scopus subject areas

  • Neuroscience(all)

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