Differential vulnerability of autonomic and somatic motor neurons to N-methyl-D-aspartate-induced excitotoxicity

Two closely-related subsets of spinal motor neurons are differentially vulnerable in the degenerative neurological disease amyotrophic lateral sclerosis. Autonomic motor neurons (i.e. preganglionic sympathetic neurons) survive in this disorder, whereas most spinal somatic motor neurons do not. The present study was undertaken in order to begin to understand the phenotypic differences between the two motor neuronal subsets which might contribute to this differential survival. Organotypic slice cultures of postnatal rat thoracic spinal cord were maintained in defined medium for one to 12 days in the presence or absence of N-methyl-D-aspartate or its antagonist, D-amino-phosphonopentanoic acid. Autonomic motor neurons that were stained for either nicotinamide adenine dinucleotide phosphate reduced diaphorase or choline acetyltransferase only were both able to tolerate 50 microM N-methyl-D-aspartate treatment for over seven days in culture with no apparent adverse effects. In contrast, cultures maintained for only one day in medium containing 50 microM N-methyl-D-aspartate showed a dramatic and highly significant decrease in the numbers of neurofilament-positive somatic motor neurons, as well as nicotinamide adenine dinucleotide phosphate reduced diaphorase-positive interneurons. These N-methyl-D-aspartate-induced effects were dose-dependent and blockable. The results of this investigation indicated that autonomic motor neurons and somatic motor neurons were differentially susceptible to N-methyl-D-aspartate-induced excitotoxicity, and that the resistance of autonomic motor neurons to this insult appeared to be independent of the nicotinamide adenine dinucleotide phosphate reduced diaphorase phenotype.