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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