Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency
نویسندگان
چکیده
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6-8 weeks genioglossus EMG and dynamic MRI of the upper airway were performed before and after administration of the DREADD ligand clozapine-N-oxide (CNO) or vehicle (saline). In DREADD-treated mice, CNO activated the genioglossus muscle and markedly dilated the pharynx, whereas saline had no effect. Control virus treated mice showed no effect of CNO. Our results suggest that chemogenetic approach can be considered as a treatment option for OSA and other motorneuron disorders.
منابع مشابه
Nicotinic excitation of rat hypoglossal motoneurons.
Hypoglossal motoneurons (HMNs), which innervate the tongue muscles, are involved in several important physiological functions, including the maintenance of upper airway patency. The neural mechanisms that affect HMN excitability are therefore important determinants of effective breathing. Obstructive sleep apnea is a disorder characterized by recurrent collapse of the upper airway that is likel...
متن کاملAnatomic consequences of intrinsic tongue muscle activation.
We recently showed respiratory-related coactivation of both extrinsic and intrinsic tongue muscles in the rat. Here, we test the hypothesis that intrinsic tongue muscles contribute importantly to changes in velopharyngeal airway volume. Spontaneously breathing anesthetized rats were placed in a MRI scanner. A catheter was placed in the hypopharynx and connected to a pressure source. Axial and s...
متن کاملBehaviors of hypoglossal hyoid motoneurons in laryngeal and vestibular reflexes and in deglutition and emesis.
Reflex responses of hypoglossal motoneurons innervating the geniohyoid (GH) and thyrohyoid (TH) muscles from the superior laryngeal (SLN) and vestibular nerves and their behaviors during fictive swallowing and vomiting were examined by recording both the extracellular activities of 11 single cells in the hypoglossal nucleus and GH and TH muscle nerve activity in eight decerebrate, paralyzed, an...
متن کاملSleep networks and the anatomic and physiologic connections with respiratory control.
A central neuronal network regulates airway functions from the nares to the bronchioles and is an integral component of a regulatory system for brain control of breathing and airway patency during wakefulness and sleep. This network, components of which include sleep generating sites and monoaminergic neurons in particular, is characterized by reciprocal interconnections, parallel organization,...
متن کاملCatecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle durin...
متن کامل