Oxytocin mediated excitation of hypoglossal motoneurons: implications for treating obstructive sleep apnea

Authors

Olga Dergacheva, Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037, USA.
Vsevolod Y. Polotsky, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
David Mendelowitz, Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037, USA.

Document Type

Journal Article

Publication Date

2-27-2023

Journal

Sleep

DOI

10.1093/sleep/zsad009

Keywords

brainstem; hypoglossal motoneurons; obstructive sleep apnea; protrudors and retractors; tongue muscles; upper airway

Abstract

Clinical studies have shown that oxytocin administered intranasally (IN) decreased the incidence and duration of obstructive events in patients with obstructive sleep apnea (OSA). Although the mechanisms by which oxytocin promotes these beneficial effects are unknown, one possible target of oxytocin could be the excitation of tongue-projecting hypoglossal motoneurons in the medulla, that exert central control of upper airway patency. This study tested the hypothesis that IN oxytocin enhances tongue muscle activity via the excitation of hypoglossal motoneurons projecting to tongue protrudor muscles (PMNs). To test this hypothesis we performed in vivo and in vitro electrophysiological studies in C57BL6/J mice as well as fluorescent imaging studies in transgenic mice in which neurons that express oxytocin receptors co-express fluorescent protein. IN oxytocin significantly increased the amplitude of inspiratory-related tongue muscle activity. This effect was abolished by severing the medial branch of hypoglossal nerve that innervates PMNs of the tongue. Oxytocin receptor-positive neurons were more prevalent in the population of PMNs than in retractor-projecting hypoglossal motoneurons (RMNs). Oxytocin administration increased action potential firing in PMNs, but had no significant effect on firing activity in RMNs. In conclusion, IN oxytocin stimulates respiratory-relating tongue muscle activity likely acting on central hypoglossal motoneurons that provide tongue protrusion and upper airway opening. This mechanism may play a role in oxytocin-induced reductions in upper airway obstructions in patients with OSA.

APA Citation

Dergacheva, Olga; Polotsky, Vsevolod Y.; and Mendelowitz, David, "Oxytocin mediated excitation of hypoglossal motoneurons: implications for treating obstructive sleep apnea" (2023). GW Authored Works. Paper 2351.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2351

Department

Pharmacology and Physiology