BRAIN-STEM MOTONEURON POOLS THAT ARE SELECTIVELY RESISTANT IN AMYOTROPHIC-LATERAL-SCLEROSIS ARE PREFERENTIALLY ENRICHED IN PARVALBUMIN - EVIDENCE FROM MONKEY BRAIN-STEM FOR A CALCIUM-MEDIATED MECHANISM IN SPORADIC ALS

Some brainstem motoneuron groups appear more resistant to the process of neurodegeneration in ALS (for example, oculomotor, trochlear, and a bducens nuclei) than others (for example, trigeminal, facial, ambiguus , and hypoglossal nuclei). The possibility that the differential prese nce of the calcium-chelating protein parvalbumin might underlie this d ifference in vulnerability was examined immunohistochemically as a way to determine whether a calcium-mediated mechanism might be involved i n ALS. In normal monkey brainstem, we found that the abundance of parv albumin-containing neurons in the oculomotor, trochlear, and abducens nuclei was approximately 90% of the abundance of choline acetyltransfe rase (CHAT)-containing motoneurons. In contrast, the abundance of parv albumin containing neurons in the other brainstem motor nuclei innerva ting skeletal muscle (trigeminal, facial, ambiguus, and hypoglossal) w as only about 30-60% of the abundance of CHAT-containing motoneurons. Since some of these motoneuron pools contain nonmotoneuron internuclea r neurons that might be parvalbumin-containing, we also carried out do uble-label studies to specifically determine the percentage of choline rgic motoneurons that contained parvalbumin in each of these motoneuro n pools. We found that 85-100% of the oculomotor, trochlear, and abduc ens motoneurons were parvalbumin-containing. In contrast, only 20-30% of the trigeminal, facial, ambiguus, and hypoglossal motoneurons were parvalbumin-containing. These results raise the possibility that moton euron death in sporadic ALS is related to some defect that promotes cy tosolic calcium accumulation in motoneurons. This excess calcium entry may promote cell death via an excitotoxic pathway. Motoneurons rich i n parvalbumin may resist the deleterious effects of this putative calc ium gating defect because they are better able to sequester the excess calcium. (C) 1995 Academic Press, Inc.