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PMID: 10725374 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death.

Grooms SY, Opitz T, Bennett MV, Zukin RS

Abstract

Kainic acid (KA)-induced status epilepticus in adult rats leads to delayed, selective death of pyramidal neurons in the hippocampal CA1 and CA3. Death is preceded by down-regulation of glutamate receptor 2 (GluR2) mRNA and protein [the subunit that limits Ca(2+) permeability of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors] in CA1 and CA3, as indicated by in situ hybridization, immunolabeling, and quantitative Western blotting. GluR1 mRNA and protein are unchanged or slightly increased before cell death. These changes could lead to formation of GluR2-lacking, Ca(2+)-permeable AMPA receptors and increased toxicity of endogenous glutamate. GluR2 immunolabeling is unchanged in granule cells of the dentate gyrus, which are resistant to seizure-induced death. Thus, formation of Ca(2+)-permeable AMPA receptors may be a critical mediator of delayed neurodegeneration after status epilepticus.

MeSH Terms
Animals Behavior, Animal Blotting, Western Cell Death/genetics Down-Regulation Hippocampus/cytology,metabolism Immunohistochemistry Male Neurons/cytology,metabolism RNA, Messenger/genetics,metabolism Rats Rats, Sprague-Dawley Receptors, Glutamate/genetics,metabolism Seizures/genetics,metabolism Status Epilepticus/genetics
Chemicals
RNA, Messenger Receptors, Glutamate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Grooms S Y
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Opitz T
Bennett M V
Zukin R S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2000-03-28
Pages
3631-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16291
Subset
IM
Grants
NINDS NIH HHS · R01 NS020752 · United States
NINDS NIH HHS · NS 20752 · United States
NINDS NIH HHS · NS 31282 · United States
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