Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study. 818 36

There is an increase in the birth of dentate granule neurons after status epilepticus (SE) and there are concurrent alterations in neurotransmitter receptor expression that may contribute to the development of spontaneous seizures. To determine whether newborn and/or mature dentate granule neurons have altered neurotransmitter receptor expression after SE, we dissected individual immature, PSA-NCAM-expressing, or mature, NeuN-expressing, dentate granule neurons 2 weeks after lithium-pilocarpine-induced SE in postnatal day 20 rats. Amplified single-cell RNA was used to probe reverse Northern blots containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate neurotransmitter receptor subunits. Two weeks after lithium-pilocarpine-induced SE there were increases in AMPA GluR2 and kainate KA2 subunit mRNA and decreases in AMPA GluR3 and kainate GluR6 receptor subunit mRNA levels in mature dentate granule neurons. In contrast, only the kainate GluR6 subunit expression was reduced in immature dentate granule neurons after SE. Alterations in transcription of excitatory amino acid receptor subunits after SE occur primarily in the mature population of dentate granule neurons. Our findings suggest that neurotransmitter receptor gene expression is altered differently in immature and mature dentate granule neurons following SE, and may result in differential contributions of these two groups of dentate granule neurons to the subsequent development of epilepsy.
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PMID:Status epilepticus differentially alters AMPA and kainate receptor subunit expression in mature and immature dentate granule neurons. 1681 74

Thyroid hormones are essential for normal brain development, and multiple alterations at behavioral, cognitive, cellular, and molecular levels have been described in animals made hypothyroid during development. Here we analyzed the effect of developmental hypothyroidism in the rat on the sensitivity to kainic acid-induced limbic seizures and the expression of kainate receptors in the hippocampus. Our results show that hypothyroid rats are extremely sensitive to the proconvulsant and neurotoxic effects of kainic acid (KA). Hypothyroid rats entered in status epilepticus at a dose of KA three times lower than that required to reach status epilepticus in control animals. In accordance with this, high levels of glial activation and neuronal loss after low KA dose injections were observed only in the hippocampus of hypothyroid rats. These effects correlated with an increased expression of kainate receptor subunits, excluding GluR5, in the hippocampus of hypothyroid animals. The concentrations of GluR6, GluR7, KAR1, and KAR2 (ionotropic glutamate receptor subunits of the kainic acid subtype) mRNAs were increased between 50 and 250% in hypothyroid animals relative to the values in controls. In agreement with these results, Western blot and immunohistochemical analysis showed a clear increase in the hippocampal content of GluR6/7 proteins in hypothyroid animals.
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PMID:Developmental hypothyroidism increases the expression of kainate receptors in the hippocampus and the sensitivity to kainic acid-induced seizures in the rat. 2041 Feb 4