GABA(A) receptor subunits in the rat hippocampus .3. Altered messenger RNA expression in kainic acid-induced epilepsy

Kainic acid-induced seizures in rats represent an established animal model for human temporal lobe epilepsy, The neuropathological sequelae include acute status epilepticus followed by neurodegeneration in the CA1 and CA3 sector of the Ammon's horn and of interneurons in the hilus of the dentate gyrus. After about three weeks spontaneous recurrent seizures become manifest. We investigated changes in messenger RNA expression of 13 GABA(A) receptor subunits in the hippocampus of rats in the initial phase (6 h, 12 h and 24 h) after acute kainic acid-induced status epilepticus and seizure-related neuronal cell damage during and after acquisition of spontaneous recurrent seizures (seven and 30 days after kainic acid injection). In the granule cell layer. initial (after 6 to 12 h) decreases in (alpha(2), alpha(3), alpha(5), beta(1), beta(3), gamma(2) and delta messenger RNAs (by about 25 to 50%) were accompanied by increases (by about 50%) in alpha(1), alpha(4), and beta(2) messages. At later intervals (after seven to 30 days), expression of alpha(2), alpha(4), beta(3) and gamma(2) messenger RNAs recovered to control values, with alpha(5) and delta messenger RNA still being reduced (by 15 and 40% below control levels, respectively). Concentrations of the transcripts encoding for alpha(1), alpha(3), beta(1), beta(2), became markedly enhanced (between 20 and 50% of controls). Within the pyramidal cell layers CAI and CA3, decreases in alpha(2), alpha(4), alpha(5), beta(1-3) and gamma(2) messenger RNAs were detected after seven to 30 days, reflecting pronounced neurodegeneration in these areas. The alpha(1) transcript was decreased in CA3 after 24 h and increased to control levels indicating compensatory up-regulation of this message after seven days. Messenger RNAs encoding for alpha(3)-, gamma(1)-, and gamma(3)-subunits were detected at rather low levels; alpha(6) was not present in the hippocampus. Our data suggest a Fast bur transient change in the expression of messenger RNAs encoding for different subunits of the GABA(A) receptor in the granule cell layer of the dentate gyrus. This is followed by a lasting augmentation of messenger RNAs encoding different GABA(A) receptor subunits in the same cell laver indicating long-lasting GABAergic inhibition. Changes within the pyramidal cell layer are mostly determined by concomitant neurodegenerative processes. (C) 1997 IBRO. Published by Elsevier Science Ltd.