HIPPOCAMPAL LOSS OF N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT-1 MESSENGER-RNA IN CHRONIC TEMPORAL-LOBE EPILEPSY

The hippocampal distribution of mRNA for the N-methyl-D-aspartate (NMD A) receptor subunit 1 (NR1) was examined by non-radioactive in situ hy bridization in 21 archival formalin-fixed and paraffin-embedded surgic al specimens from patients with pharmacoresistant chronic epilepsy and in normal control specimens obtained at autopsy. Using the digoxigeni n-labeling procedure, ribonucleotide probes were found to be significa ntly more sensitive than synthetic oligonucleotide probes. In normal a utopsy specimens and in surgical specimens without Ammon's horn sclero sis there was intense NR1 expression in a great majority of the dentat e 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 gyru s contained only few labeled neurons. In the subiculum and entorhinal cortex most neurons throughout various layers were positive. In hippoc ampal specimens of patients with chronic epilepsy there was a loss of NR1-positive cells that was closely related to the overall neuronal lo ss in the respective specimen and to Ammon's horn sclerosis. These dat a suggest that the loss of NR1 expression is a secondary phenomenon ra ther than an event that is relevant for the pathogenesis of epileptic seizures.