Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) rec eptor (NMDAR) alters its channel properties, and may enhance or reduce neur onal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or de creased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hi ppocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by us ing semiquantitative in situ hybridization techniques, along with neuron de nsities. Compared with autopsy hippocampi, non-HS and HS patients showed in creased NR2A and NR2B hybridization densities per dentate granule cell. Fur thermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per C A2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast , showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chroni c temporal lobe seizures are associated with differential changes in hippoc ampal NR1 and NR2A-D hybridization densities that vary by subfield and clin ical-pathological category. In temporal lobe epilepsy patients, these findi ngs support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, sh owed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NM DA-mediated pyramidal neuron responses should be reduced in MS patients com pared with non-HS cases.