Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency

Thomaz Fleury Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, Luiz U. Sennes, Luu V. Pham, Ellen E. Ladenheim, Richard Spencer, David Mendelowitz, Alan R. Schwartz, Vsevolod Y. Polotsky

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number44392
JournalScientific reports
Volume7
DOIs
StatePublished - Mar 10 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency'. Together they form a unique fingerprint.

Cite this