EXPRESSION OF N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT MESSENGER-RNA IN THE HUMAN BRAIN - MESENCEPHALIC DOPAMINERGIC-NEURONS

Evidence is accumulating that glutamate-mediated excitotoxicity plays an important role in neuronal degeneration in Parkinson's disease (PD) . In addition, alterations in excitatory amino acid neurotransmission in the basal ganglia contribute to the clinical manifestations of moto r dysfunction. However, detailed knowledge of the anatomical distribut ion and subtype specificity of glutamate receptors in the dopamine neu rons of human substantia nigra (SN) has been lacking, In order to test the hypothesis that selective expression of particular N-methyl-D-asp artate receptor (NR) subunit mRNA contributes to the differential vuln erability of specific neuronal populations to excitotoxic injury in PD , we have used a quantitative dual label, in situ hybridization techni que with ribonucleotide probes to examine the cellular distribution of NR subunit mRNA in postmortem human mesencephalic dopaminergic neuron s from subjects with no known neurological disorder. Analysis of both film autoradiograms and emulsion-dipped sections demonstrated signific ant labeling of nigral neurons for each NR subunit. Neuronal labeling was most intense for the NR1 and NR2D subunits, with low level labelin g for the remaining subunits. In addition, we examined four subregions of the ventral mesencephalon for differential expression of NR subuni t mRNA. For all NR subunits, the pars lateralis (PL) exhibited the mos t intense signal, while neurons of the ventral tier substantia nigra p ars compacta (SNpc) failed to demonstrate a preponderance of a particu lar subunit. These results demonstrate that NRs are expressed to a sig nificant degree in dopaminergic neurons of the SN and that their distr ibution does not correlate with the characteristic pattern of neuronal degeneration in PD. (C) 1998 Wiley-Liss. Inc.