Differential vulnerability of two subsets of spinal motor neurons in amyotrophic lateral sclerosis

The primary objective of this study was to determine the pattern of motor neuron loss in thoracic spinal cord from amyotrophic lateral sclerosis (ALS) patients. A prerequisite to this objective was to examine control human spinal cord with the techniques to be used for ALS specimens. Combined choline acetyltransferase (ChAT) immunocytochemistry and NADPH diaphorase histochemistry (a marker for nitric oxide synthase) revealed a staining pattern very similar to that seen in other mammals. Stained cell groups were present in the superficial dorsal horn (labeled only by diaphorase), the deep dorsal horn (double-labeled), the intermediate region (double-labeled), around the central canal (mostly double-labeled), autonomic motor neurons (AMNs; either double-labeled or ChAT-positive only), and somatic motor neurons (SMNs; ChAT-positive only). These similarities indicated that most cell types previously described in other mammals are present in human spinal cord. However, the percentage of AMNs that were double-labeled was much higher in humans (94%) than in rodents (approximately 66%) or in nonmammalian vertebrates (essentially 0%). In ALS, extensive loss of SMNs is known to occur in cervical and lumbar enlargements, and similarly, our specimens revealed a degeneration of nearly all SMNs in thoracic spinal cord. In contrast, the average number of AMNs in ALS specimens was not significantly different from that in controls, directly confirming clinical observations suggesting that AMNs do not degenerate in ALS. Most importantly, the percentage of AMNs that were diaphorase-negative was not decreased in ALS, indicating that AMN resistance in this degenerative neurological disorder probably is independent of nitric oxide synthase expression.