Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency

Sci Rep. 2017 Mar 10;7:44392. doi: 10.1038/srep44392.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Clozapine / analogs & derivatives*
  • Clozapine / pharmacology
  • Dependovirus / genetics
  • Dependovirus / metabolism
  • Disease Models, Animal
  • Electromyography
  • Genes, Reporter
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hypoglossal Nerve / drug effects*
  • Hypoglossal Nerve / metabolism
  • Hypoglossal Nerve / physiopathology
  • Injections, Intraventricular
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Pharynx / diagnostic imaging
  • Pharynx / drug effects*
  • Pharynx / innervation
  • Pharynx / metabolism
  • Sleep Apnea, Obstructive / diagnostic imaging
  • Sleep Apnea, Obstructive / metabolism
  • Sleep Apnea, Obstructive / physiopathology
  • Sleep Apnea, Obstructive / therapy*
  • Stereotaxic Techniques


  • Antipsychotic Agents
  • Luminescent Proteins
  • enhanced green fluorescent protein
  • red fluorescent protein
  • Green Fluorescent Proteins
  • Clozapine
  • clozapine N-oxide