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J Neurosci. 1994 May;14(5 Pt 1):2697-707.

Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study.

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  • 1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.

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 GABAA 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 Ca(2+)-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABAA alpha 1, 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 GABAA alpha 1 mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABAA alpha 1 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 GABAA receptor expression in a cell-specific manner. Timing of the changes in glutamate and GABAA receptor mRNAs indicates that these changes may play a causal role in hippocampal neuronal cell loss following kainate-induced seizures.

PMID:
8182436
[PubMed - indexed for MEDLINE]
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