title: Brainstem motoneuron pools that are selectively resistant in amyotrophic lateral sclerosis are preferentially enriched in parvalbumin: evidence from monkey brainstem for a calcium-mediated mechanism in sporadic ALS.
abstract: Some brainstem motoneuron groups appear more resistant to the process of neurodegeneration in ALS (for example, oculomotor, trochlear, and abducens nuclei) than others (for example, trigeminal, facial, ambiguus, and hypoglossal nuclei). The possibility that the differential presence of the calcium-chelating protein parvalbumin might underlie this difference in vulnerability was examined immunohistochemically as a way to determine whether a calcium-mediated mechanism might be involved in ALS. In normal monkey brainstem, we found that the abundance of parvalbumin-containing neurons in the oculomotor, trochlear, and abducens nuclei was approximately 90% of the abundance of choline acetyltransferase (CHAT)-containing motoneurons. In contrast, the abundance of parvalbumin-containing neurons in the other brainstem motor nuclei innervating skeletal muscle (trigeminal, facial, ambiguus, and hypoglossal) was only about 30-60% of the abundance of CHAT-containing motoneurons. Since some of these motoneuron pools contain nonmotoneuron internuclear neurons that might be parvalbumin-containing, we also carried out double-label studies to specifically determine the percentage of cholinergic motoneurons that contained parvalbumin in each of these motoneuron pools. We found that 85-100% of the oculomotor, trochlear, and abducens 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 motoneuron death in sporadic ALS is related to some defect that promotes cytosolic calcium accumulation in motoneurons. This excess calcium entry may promote cell death via an excitotoxic pathway. Motoneurons rich in parvalbumin may resist the deleterious effects of this putative calcium gating defect because they are better able to sequester the excess calcium.
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee at Memphis 38163, USA.
authors.forename: A
authors.initials: A
authors.lastname: Reiner
authors.forename: L
authors.initials: L
authors.lastname: Medina
authors.forename: G
authors.initials: G
authors.lastname: Figueredo-Cardenas
authors.forename: S
authors.initials: S
authors.lastname: Anfinson
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000737:chemistry*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D016923:Cell Death; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003391:Cranial Nerves / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D015640:Ion Channel Gating; D008253:Macaca mulatta / Q000033:anatomy & histology / Q000378:metabolism; D009046:Motor Neurons / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009498:Neurotoxins / Q000378:metabolism; D010320:Parvalbumins / Q000032:analysis*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D010320:Parvalbumins; D002795:Choline O-Acetyltransferase; D002118:Calcium