Document Type
Journal Article
Publication Date
3-2017
Journal
Scientific Reports
Volume
7
Inclusive Pages
44392
DOI
10.1038/srep44392
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Curado, T., Fishbein, K., Pho, H., Brennick, M., Dergacheva, O., Mendelowitz, D., & +several additional authors (2017). Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency. Scientific Reports, 7 (). http://dx.doi.org/10.1038/srep44392
Peer Reviewed
1
Open Access
1
Included in
Medical Pharmacology Commons, Medical Physiology Commons, Otorhinolaryngologic Diseases Commons, Pharmacology Commons, Physiology Commons, Translational Medical Research Commons
Comments
Reproduced with permission of Macmillan Publishers Ltd. Scientific Reports