Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death.
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.
Grooms
S Y
SY
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Opitz
T
T
Bennett
M V
MV
Zukin
R S
RS
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics*; D015536:Down-Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000235:genetics / Q000378:metabolism; D013226:Status Epilepticus / Q000235:genetics*
D012333:RNA, Messenger; D017470:Receptors, Glutamate