Changes in glutamate receptor and proenkephalin gene expression after kindled seizures

Lee, Sooja; Miskovsky, John; Williamson, John; Howells, Richard D.; Devinsky, Orrin; Lothman, Eric W.; Christakos, Sylvia

doi:10.1016/0169-328x(94)90115-5

Cited by 42 publications

(13 citation statements)

References 58 publications

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“…It is also noteworthy that intraperitoneal administration of kainate leads to edema/ischemia (Sperk et al, 1983), and ischemia has been reported to decrease the hippocampal GluR2 mRNA level after 24h Pollard et al, 1993). As regards other models of the temporal lobe of epilepsy, hippocampal kindling increased the expression of the flip, but not the flop, variant of GluR1 and GluR2 mRNAs in the dentate gyrus (Kamphuis et al, 1992), whereas amygdalar kindling decreased the GluR2 mRNA level in the rat hippocampus (Gold et al, 1996;Lee et al, 1994). The kindling-, pilocarpine-and kainate-induced seizures enhance glutamate transmission in the hippocampus (Arias et al, 1990;Croucher et al, 1988;Turski et al, 1989), thus the down-regulation of the GluR2 mRNA level may be regarded as an adaptive response to an oversupply of the agonist.…”

Section: Discussionmentioning

confidence: 97%

Seizure-related changes in the glutamate R2 and R5 receptor genes expression in the rat hippocampal formation

Lasoń

Turchan

Przewłocka

et al. 1997

J. Neural Transmission

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The expression of mRNA coding for AMPA selective glutamate (Glu) R2 receptor and kainate selective GluR5 receptor was studied in the rat hippocampal formation in two animal models of limbic seizures evoked by systemic administration of pilocarpine (400 mg/kg i.p.) or kainate (15 mg/kg i.p.). As shown by an in situ hybridization study, pilocarpine decreased the GluR2 flip mRNA level in CA1 and CA3 areas of the hippocampus after 3h and kainate after 24h, e.g. at the time preceding neuronal degeneration. No changes in the GluR2 flop or GluR5 mRNA level were found in those regions. In the dentate gyrus, resistant to neurodegeneration, pilocarpine and kainate differentially affected the expression of GluR2 and GluR5 mRNAs. After 72h pilocarpine, but not kainate, increased the GluR2 flop mRNA level and decreased the flip one, which suggests attenuation of the GluR2 sensitivity. On the other hand, kainate, elevated the GluR2 flip and GluR5 mRNA level in the dentate gyrus after 72h. All in all the above data suggest that changes in the GluR2 gene expression may play some role in the neuronal damage to vulnerable areas (CA1, CA3). However, differences in the kainate-and pilocarpine-induced changes in the dentate gyrus at the late time points indicate that alterations in the stoichiometry of GluR2 forms of GluR5 gene expression in this brain region are not a common causal factor responsible for delayed neuronal hyperexcitability.

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Section: Discussionmentioning

confidence: 97%

Seizure-related changes in the glutamate R2 and R5 receptor genes expression in the rat hippocampal formation

Lasoń

Turchan

Przewłocka

et al. 1997

J. Neural Transmission

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“…For example, several reports have characterized changes in rat hippocampal AMPA and NMDA hybridization densities within hours to a few days following injury or seizures induced from kainate, pilocarpine, limbic kindling, electrolytic lesions, electroshock, intracerebral needle insertion, and stressful handling (Gall et al, 1990;Kamphuis et al, 1992Kamphuis et al, , 1994Kamphuis et al, , 1995Pollard et al, 1993;Pratt et al, 1993;Wong et al, 1993;Condorelli et al, 1994;Friedman et al, 1994Friedman et al, , 1997Kraus et al, 1994;Lee et al, 1994;Bartanusz et al, 1995;Prince et al, 1995;Gold et al, 1996;Naylor et al, 1996;Lason et al, 1997). These stimuli result in mild agitation or injury without seizures (handling and needle insertion), a few limbic seizures over several hours (electrolytic and electroshock), multiple reactive seizures spaced over days to weeks (kindling), or near-lethal status epilepticus (kainate and pilocarpine).…”

Section: Comparison With Prior Animal and Human Studiesmentioning

confidence: 99%

Hippocampal AMPA and NMDA mRNA levels correlate with aberrant fascia dentata mossy fiber sprouting in the pilocarpine model of spontaneous limbic epilepsy

et al. 1998

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There is considerable controversy whether aberrant fascia dentata (FD) mossy fiber sprouting is an epiphenomena related to neuronal loss or a pathologic abnormality responsible for spontaneous limbic seizures. If mossy fiber sprouting contributes to seizures, then reorganized axon circuits should alter postsynaptic glutamate receptor properties. In the pilocarpine-status rat model, this study determined if changes in alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and n-methyl-D-aspartic acid (NMDA) receptor subunit mRNA levels correlated with mossy fiber sprouting. Sprague-Dawley rats were injected with pilocarpine (320 mg/kg; i.p.) and maintained in status epilepticus for 6 to 8 hours (pilocarpine-status). Rats were killed during the: (1) latent phase after neuronal loss but before spontaneous limbic seizures (day 11 poststatus; n = 7); (2) early seizure phase after their first seizures (day 25; n = 7); and (3) chronic seizure phase after many seizures (day 85; n = 9). Hippocampi were studied for neuron counts, inner molecular layer (IML) neo-Timm's staining, and GluR1-3 and NMDAR1-2b mRNA levels. Compared with controls, pilocarpine-status rats in the: (1) latent phase showed increased FD GluR3, NMDAR1, and NMDAR2b; greater CA4 and CA1 NMDAR1; and decreased subiculum GluR1 hybridization densities; (2) early seizure phase showed increased FD GluR3, increased CA1 NMDAR1, and decreased subiculum NMDAR2b densities; and (3) chronic seizure phase showed increased FD GluR2; increased FD and CA4 GluR3; decreased CA1 GluR2; and decreased subiculum GluR1, GluR2, NMDAR1, and NMDAR2b levels. In multivariate analyses, greater IML neo-Timm's staining: (1) positively correlated with FD GluR3 and NMDAR1 and (2) negatively correlated with CA1 and subiculum GluR1 and GluR2 mRNA levels. These results indicate that: (1) hippocampal AMPA and NMDA receptor subunit mRNA levels changed as rats progressed from the latent to chronic seizure phase and (2) certain subunit alterations correlated with mossy fiber sprouting. Our findings support the hypothesis that aberrant axon circuitry alters postsynaptic hippocampal glutamate receptor subunit stoichiometry; this may contribute to limbic epileptogenesis.

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“…Friedman et al investigated the effects of kainate induced seizures on al levels; 24 h after the seizures had started, a reduction of ~1 was found in CA3 and no changes in CA1 or fascia dentata [11]. A Northern and slot blot analysis of mRNA from several brain regions failed to find any significant changes in al, a2, a4 or/31 transcripts, 30 days after hippocampal kindling or 24 h after rapid kindling [31]. Recently, an enhanced expression of a4, /31 and /33 subunits in the fascia dentata, 4 h after the last amaygdala kindling induced seizure, was reported [6].…”

Section: Gaba Ar Subunit Mrna Expression In Other Models Of Synaptic mentioning

confidence: 99%

Expression of GABAA receptor subunit mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study

Kamphuis

Rijk

Silva

1995

Molecular Brain Research

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Expression of GABA-A receptor subunit in mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study. Kamphuis, W.; de Rijk, T.C.; Lopes da Silva, F.H. Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Accepted 24 January 1995 AbstractTo investigate the molecular changes underlying kindling epileptogenesis in the rat hippocampus, the expression levels of the genes encoding for 13 different y-aminobutyric acid type-A receptor (GABAAR) subunits were measured in hippocampal principal neurons using in situ hybridization techniques and semi-quantitative analysis of the autoradiograms. Schaffer collateral-commissural pathway kindled rats were investigated at three different stages of kindling acquisition, at 24 h after the last seizure and at long-term (28 days) after termination of kindling stimulations. Changes were distinct for the different subunits in the three analyzed regions (CA1, CA3, fascia dentata) and also different for the various kindling stages. In all hippocampal areas at the early phases of kindling epileptogenesis, before the appearance of generalized seizures, an increase was found of those transcripts that constituted the majority of the expressed variants in control animals (al, a2, a4, /31, /32, /33, y2/y2L mRNA). In these stages, the increased levels of different variants in the granular neurons of the fascia dentata were more pronounced when compared to the pattern of changes in pyramidal cells of CA1 and CA3. In fully kindled animals, the expression levels of several subunits returned to control levels, whereas/33 and y2/y2L mRNA expression was still significantly enhanced in all areas. At long-term, few changes were encountered. The long-splice variant of 3,2 was decreased within pyramidal and granular neurons while the total level of y2 mRNA was not different from controls. The increased GABAAR subunit expression in the fascia dentata may underly the reported increased GABAAR ligand binding and the increased GABA mediated inhibition. However, the decreased GABAAR binding and the attenuation of GABAergic inhibition in CA1, could not be explained by a decrement of receptor subunit expression.

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Changes in glutamate receptor and proenkephalin gene expression after kindled seizures

Cited by 42 publications

References 58 publications

Seizure-related changes in the glutamate R2 and R5 receptor genes expression in the rat hippocampal formation

Seizure-related changes in the glutamate R2 and R5 receptor genes expression in the rat hippocampal formation

Hippocampal AMPA and NMDA mRNA levels correlate with aberrant fascia dentata mossy fiber sprouting in the pilocarpine model of spontaneous limbic epilepsy

Expression of GABAA receptor subunit mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study

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