Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy
1 Department of Neurology Rochester, MN, USA 2 Division of Anatomic Pathology, Mayo Clinic Rochester, MN, USA
Correspondence to: Eduardo E. Benarroch, MD, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA E-mail: benarroch.eduardo{at}mayo.edu
Multiple system atrophy (MSA) is a disorder that may manifest with reduced respiratory chemosensitivity and central sleep apnoea. Chemosensitive glutamatergic and serotonergic neurons located just beneath the ventral medullary surface, corresponding to the human arcuate nucleus (ArcN), have recently been implicated in control of automatic breathing in response to hypercapnia and hypoxia. We sought to determine whether these neurons were affected in MSA. Medullae were obtained at post-mortem from 11 patients (8 men, 3 women, age 64 ± 3 years) with neuropathologically confirmed MSA and 11 control subjects (6 men and 5 women, age 66 ± 4 years). Fifty micrometre sections obtained throughout the medulla were processed for vesicular glutamate transporter-2 (VGLUT-2), tryptophan-hydroxylase (TrOH), glial fibrillary acid protein (GFAP) and 
-synuclein immunoreactivity. Cell counts, GFAP immunoreactivity and presence of glial cytoplasmic inclusions (GCIs) were assessed in the ArcN. In MSA, compared with controls, there was a marked depletion of ArcN neurons immunoreactive for either VGLUT-2 (74 ± 21 versus 342 ± 84 cells/section, P < 0.004) or TrOH (5 ± 1 versus 16 ± 2 cells/section, P < 0.001). There was also marked astrocytic gliosis and accumulation of -synuclein immunoreactive GCIs in the ventral medullary surface in all cases. Our results indicate that there is severe loss of putative chemosensitive glutamatergic and serotonergic neurons as well as marked astrocytic gliosis in the ventral medullary surface in MSA. This may provide a possible morphological basis for impaired respiratory chemosensitivity and central sleep apnoea in this disorder.
Key Words: arcuate nucleus; glutamate; serotonin; respiration; apnoea
Abbreviations: ArcN, arcuate nucleus; GCI, glial cytoplasmic inclusion; MSA, multiple system atrophy; OSA, obstructive sleep apnoea; TrOH, tryptophan hydroxylase; VGLUT-2, vesicular glutamate transporter-2
Received September 21, 2006. Revised October 27, 2006. Accepted November 28, 2006.
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