HIPPOCAMPAL AMPA AND NMDA MESSENGER-RNA LEVELS AND SUBUNIT IMMUNOREACTIVITY IN HUMAN TEMPORAL-LOBE EPILEPSY PATIENTS AND A RODENT MODEL OF CHRONIC MESIAL LIMBIC EPILEPSY

This study compared temporal lobe epilepsy patients, along with kindle d animals and self sustained limbic status epilepticus (SSLSE) rats fo r parallels in hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis patients CHS), non-HS cases, and autopsies were studied for: hippocampal AMPA GluR1-3 and NM-DAR1&2b mRNA levels using in situ hybridization; GluR1, GluR2/3, NMDAR1, and NMDAR2(a&b) immuno reactivity (IR); and neuron densities. Similarly, spontaneously seizin g rats after SSLSE, kindled rats, and control animals were studied for : fascia dentata neuron densities; GluR1 and NMDAR2(a&b) IR; and neo-T imm's staining. In MS and non-HS cases, the mRNA hybridization densiti es per granule cell, as well as molecular layer IR, showed increased G luR1 (relative to GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies. Likewise, the molecular layer of SSLSE rats wit h spontaneous seizures demonstrated more neo-Timm's staining;, and hig her levels of GluR1 and NMDAR2(a&b) IR compared to kindled animals and controls. These results indicate that hippocampal AMPA and NMDA recep tor subunit mRNAs and their proteins are differentially increased in a ssociation with spontaneous, but not kindled, seizures. Furthermore, t here appears to be parallels in fascia dentata AMPA and NMDA receptor subunit expression between HS land non-HS) epileptic patients and SSLS E rats. This finding supports the hypothesis that spontaneous seizures in humans and SSLSE rats involve differential alterations in hippocam pal ionotrophic glutamate receptor subunits. Moreover, non-HS hippocam pi were more like HS cases than hippocampi from kindled animals with r espect to glutamate receptors; therefore, hippocampi from kindled rats do not accurately model human non-HS cases, despite some similarities in neuron densities and mossy fiber axon sprouting. (C) 1998 Elsevier Science B.V. All rights reserved.