Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy

Mathern, Gary W; Pretorius, James K; Leite, Joao P; Kornblum, Harley I; Mendoza, Delia; Lozada, Alana; Bertram III, Edward H

« Previous Next »Epilepsy Research
Volume 32, Issue 1 , Pages 154-171, 1 September 1998

Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy

Gary W Mathern
- Division of Neurosurgery, Reed Neurological Research Center, UCLA Medical Center, Los Angeles, CA 90095-1769, USA
- The Brain Research Institute, University of California–Los Angeles, Los Angeles, CA 90095, USA
- Corresponding author. Tel.: +1 310 2068777; fax: +1 310 2068461; e-mail: gmathern@ucla.edu
James K Pretorius
- The Brain Research Institute, University of California–Los Angeles, Los Angeles, CA 90095, USA
Joao P Leite
- Department of Neurology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto (SP), Brazil
Harley I Kornblum
- Department of Pediatrics, University of California–Los Angeles, Los Angeles, CA 90095, USA
- Department of Molecular and Medical Pharmacology, University of California–Los Angeles, Los Angeles, CA 90095, USA
- The Brain Research Institute, University of California–Los Angeles, Los Angeles, CA 90095, USA
Delia Mendoza
- The Brain Research Institute, University of California–Los Angeles, Los Angeles, CA 90095, USA
Alana Lozada
- The Brain Research Institute, University of California–Los Angeles, Los Angeles, CA 90095, USA
Edward H Bertram III
- Department of Neurology, University of Virginia, Charlottesville, VA, USA

Abstract

This study compared temporal lobe epilepsy patients, along with kindled animals and self sustained limbic status epilepticus (SSLSE) rats for parallels in hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis patients (HS), non-HS cases, and autopsies were studied for: hippocampal AMPA GluR1-3 and NMDAR1&2b mRNA levels using in situ hybridization; GluR1, GluR2/3, NMDAR1, and NMDAR2_a&b immunoreactivity (IR); and neuron densities. Similarly, spontaneously seizing rats after SSLSE, kindled rats, and control animals were studied for: fascia dentata neuron densities; GluR1 and NMDAR2_a&b IR; and neo-Timm's staining. In HS and non-HS cases, the mRNA hybridization densities per granule cell, as well as molecular layer IR, showed increased GluR1 (relative to GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies. Likewise, the molecular layer of SSLSE rats with spontaneous seizures demonstrated more neo-Timm's staining, and higher levels of GluR1 and NMDAR2_a&b IR compared to kindled animals and controls. These results indicate that hippocampal AMPA and NMDA receptor subunit mRNAs and their proteins are differentially increased in association with spontaneous, but not kindled, seizures. Furthermore, there appears to be parallels in fascia dentata AMPA and NMDA receptor subunit expression between HS (and non-HS) epileptic patients and SSLSE rats. This finding supports the hypothesis that spontaneous seizures in humans and SSLSE rats involve differential alterations in hippocampal ionotrophic glutamate receptor subunits. Moreover, non-HS hippocampi were more like HS cases than hippocampi from kindled animals with respect 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.

Keywords: Excitatory amino acid receptors, Complex partial seizures, Human hippocampi, Rat models