Loss of putative GABAergic neurons in the ventrolateral medulla in multiple system atrophy

Abstract

Study objectives: Multiple system atrophy (MSA) is associated with disturbances in cardiovascular, sleep and respiratory control. The lateral paragigantocellular nucleus (LPGi) in the ventrolateral medulla (VLM) contains GABAergic neurons that participate in control of rapid eye movement (REM) sleep and cardiovagal responses. We sought to determine whether there was loss of putative GABAergic neurons in the LPGi and adjacent regions in MSA.

Methods: Sections of the medulla were processed for GAD65/67 immunoreactivity in eight subjects with clinical and neuropathological diagnosis of MSA and in six control subjects. These putative GABAergic LPGi neurons were mapped based on their relationship to adjacent monoaminergic VLM groups.

Results: There were markedly decreased numbers of GAD-immunoreactive neurons in the LPGi and adjacent VLM regions in MSA.

Conclusions: There is loss of GABAergic neurons in the VLM, including the LPGi in patients with MSA. Whereas these findings provide a possible mechanistic substrate, given the few cases included, further studies are necessary to determine whether they contribute to REM sleep-related cardiovagal and possibly respiratory dysregulation in MSA.

Keywords: Lateral paragigantocellular nucleus; REM sleep; alpha-synuclein; autonomic; cardiovagal multiple system atrophy; orthostatic hypotension.