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

Linda K. Friedman, Domenico E. Pellegrini-Giampietro, Ellen F. Sperber, Michael V. L. Bennett, Solomon L. Moshe, R. Suzanne Zukin

Research output: Contribution to journalArticle

233 Citations (Scopus)

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 Ca2+-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABA1 a, 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 GluRS expression were observed; GluR 1, NR1, and GABAA a, mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABA4α1, 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.

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

Fingerprint

Status Epilepticus
Kainic Acid
Glutamate Receptors
GABA-A Receptors
In Situ Hybridization
Hippocampus
Dentate Gyrus
Gene Expression
Kainic Acid Receptors
Seizures
Messenger RNA
Glutamic Acid
Hippocampal CA3 Region
AMPA Receptors
Temporal Lobe Epilepsy
Neurotoxins
Emulsions
Virulence
Permeability
Neurons

Keywords

  • AMPA receptors
  • Epilepsy
  • Kainate receptors
  • NMDA receptors
  • Receptor mRNAs
  • Seizures

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus : An in situ hybridization study. / Friedman, Linda K.; Pellegrini-Giampietro, Domenico E.; Sperber, Ellen F.; Bennett, Michael V. L.; Moshe, Solomon L.; Zukin, R. Suzanne.

In: Journal of Neuroscience, Vol. 14, No. 5 I, 05.1994, p. 2697-2707.

Research output: Contribution to journalArticle

@article{70192115b64748a6b910b7f8ee851143,
title = "Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: An in situ hybridization study",
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 Ca2+-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABA1 a, 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 GluRS expression were observed; GluR 1, NR1, and GABAA a, mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABA4α1, 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.",
keywords = "AMPA receptors, Epilepsy, Kainate receptors, NMDA receptors, Receptor mRNAs, Seizures",
author = "Friedman, {Linda K.} and Pellegrini-Giampietro, {Domenico E.} and Sperber, {Ellen F.} and Bennett, {Michael V. L.} and Moshe, {Solomon L.} and Zukin, {R. Suzanne}",
year = "1994",
month = "5",
language = "English (US)",
volume = "14",
pages = "2697--2707",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5 I",

}

TY - JOUR

T1 - Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus

T2 - An in situ hybridization study

AU - Friedman, Linda K.

AU - Pellegrini-Giampietro, Domenico E.

AU - Sperber, Ellen F.

AU - Bennett, Michael V. L.

AU - Moshe, Solomon L.

AU - Zukin, R. Suzanne

PY - 1994/5

Y1 - 1994/5

N2 - 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 Ca2+-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABA1 a, 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 GluRS expression were observed; GluR 1, NR1, and GABAA a, mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABA4α1, 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.

AB - 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 Ca2+-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABA1 a, 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 GluRS expression were observed; GluR 1, NR1, and GABAA a, mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABA4α1, 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.

KW - AMPA receptors

KW - Epilepsy

KW - Kainate receptors

KW - NMDA receptors

KW - Receptor mRNAs

KW - Seizures

UR - http://www.scopus.com/inward/record.url?scp=0028202875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028202875&partnerID=8YFLogxK

M3 - Article

C2 - 8182436

AN - SCOPUS:0028202875

VL - 14

SP - 2697

EP - 2707

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 5 I

ER -