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 pr otein [the subunit that limits Ca2+ permeability of alpha-amino-3-hydroxy-5 -methyl-4-isoxazolepropionic acid (AMPA) receptors] in CA1 and CA3, as indi cated by in situ hybridization, immunolabeling, and quantitative Western bl otting. GluR1 mRNA and protein are unchanged or slightly increased before c ell death. These changes could lead to formation of GluR2-lacking, Ca2+-per meable AMPA receptors and increased toxicity of endogenous glutamate. GluR2 immunolabeling is unchanged in granule cells of the dentate gyrus, which a re resistant to seizure-induced death. Thus, formation of Ca2+-permeable AM PA receptors may be a critical mediator of delayed neurodegeneration after status epilepticus.