Depletion of cholinergic neurons of the medullary arcuate nucleus in multiple system atrophy

The human arcuate nucleus (ArcN) has been considered akin to the pontine pr ecerebellar nuclei. However, there is anatomical, functional, and clinical evidence that the ArcN may be the homologue of chemosensitive areas of the ventral medullary surface involved in ventilatory responses to hypercarbia and cerebrospinal fluid acidosis. Acetylcholine has been involved in mechan isms of central chemosensitivity. Loss of ArcN neurons has been reported in patients with multiple system atrophy (MSA), a disorder characterized by d isturbed automatic ventilation, but the neurochemical identity of these neu rons is undetermined. We sou ht to determine whether the ArcN contains chol inergic neurons and whether these neurons are depleted in patients with MSA . Medullae were obtained from six patients with MSA, five patients with Par kinson's disease (PD) and six sex- and age-matched controls. Fifty-micron t ransverse sections obtained through the mid-olivary levels were processed f or acetylcholinesterase (AchE), choline acetyltransferase (CAT), and alpha -synuclein immunoreactivity. We found that the ArcN contained CAT-positive neurons. There was a significant decrease in density of cholinergic ArcN ne urons in MSA but not in PD patients, alpha -Synuclein-containing inclusions were present in the ArcN of MSA patients. Depletion of cholinergic neurons may provide a substrate for disturbances in automatic respiration in MSA p atients. (C) 2001 Elsevier Science B.V. All rights reserved.