Cortical and striatal neuronal cultures of the same embryonic origin show intrinsic differences in glutamate receptor expression and vulnerability toexcitotoxicity

Cortical and striatal cultures were prepared from the same embryonic rat br ains and maintained in identical culture conditions. In this way, the intri nsic, genetically imprinted differences determine the responses of cortical and striatal neurons in comparative studies. Cortical and striatal neurons differed in their sensitivity to glutamate receptor-mediated neurotoxicity as measured by the MTT cell viability assay. On the 8th day in vitro, stri atal cultures were less sensitive to N-methyI-D-aspartate (NMDA)-induced to xicity than cortical, although both cultures mere equally vulnerable to alp ha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)- or kainate-induc ed toxicity. The AMPA receptor-mediated cell death in cortical cultures, ho wever, was much more dependent on preventing AMPA receptor desensitization than in striatal cultures. Furthermore, glutamate-induced neurotoxicity was primarily mediated by NMDA receptors in cortical cultures, while blockade of either NMDA or AMPA receptors gave almost complete protection against gl utamate in striatal cultures. To elucidate the molecular mechanisms respons ible for the observed differences, we analyzed the expression of NMDA recep tor subunits (NR1, NR2A-C) at the mRNA and the protein level in cortical an d striatal cultures as web as in standard cerebellar granule cell cultures. The lowest expression level of NMDA receptor subunits was found in striata l cultures, thereby providing a possible explanation for their lower sensit ivity to NMDA. Remarkable differences were found between the relative rates of mRNA and protein expression for NR1 and NR2B in the three cultures, ind icative of intrinsic differences in the posttranscriptional regulation of N MDA receptor subunit expression in cultures from various brain regions, (C) 2001 Academic Press.