Hippocampal loss of N-methyl-D-aspartate receptor subunit 1 mRNA in chronic temporal lobe epilepsy.

The hippocampal distribution of mRNA for the N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1) was examined by non-radioactive in situ hybridization in 21 archival formalin-fixed and paraffin-embedded surgical specimens from patients with pharmacoresistant chronic epilepsy and in normal control specimens obtained at autopsy. Using the digoxigenin-labeling procedure, ribonucleotide probes were found to be significantly more sensitive than synthetic oligonucleotide probes. In normal autopsy specimens and in surgical specimens without Ammon's horn sclerosis there was intense NR1 expression in a great majority of the dentate gyrus granular cells. Many neurons in the hippocampal pyramidal cell layer also revealed a strong signal intensity. The strata oriens and moleculare of Ammon's horn and the molecular layer of the dentate gyrus contained only few labeled neurons. In the subiculum and entorhinal cortex most neurons throughout various layers were positive. In hippocampal specimens of patients with chronic epilepsy there was a loss of NR1-positive cells that was closely related to the overall neuronal loss in the respective specimen and to Ammon's horn sclerosis. These data suggest that the loss of NR1 expression is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.