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

Eduardo E. Benarroch, Ann M. Schmeichel, Joseph E. Parisi

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The human arcuate nucleus (ArcN) has been considered akin to the pontine precerebellar 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 mechanisms of central chemosensitivity. Loss of ArcN neurons has been reported in patients with multiple system atrophy (MSA), a disorder characterized by disturbed automatic ventilation, but the neurochemical identity of these neurons is undetermined. We sought to determine whether the ArcN contains cholinergic neurons and whether these neurons are depleted in patients with MSA. Medullae were obtained from six patients with MSA, five patients with Parkinson's disease (PD) and six sex- and age-matched controls. Fifty-micron transverse sections obtained through the mid-olivary levels were processed for acetylcholinesterase (AchE), choline acetyltransferase (CAT), and α-synuclein immunoreactivity. We found that the ArcN contained CAT-positive neurons. There was a significant decrease in density of cholinergic ArcN neurons in MSA but not in PD patients. α-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 patients.

Original languageEnglish (US)
Pages (from-to)293-299
Number of pages7
JournalAutonomic Neuroscience: Basic and Clinical
Volume87
Issue number2-3
DOIs
StatePublished - Mar 23 2001

Keywords

  • Chemosensitive area
  • Choline-acetyltransferase
  • Sleep apnea

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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