Dataset Information

Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency.

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.

SUBMITTER: Fleury Curado T

PROVIDER: S-EPMC5345079 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency.

Fleury Curado Thomaz T Fishbein Kenneth K Pho Huy H Brennick Michael M Dergacheva Olga O Sennes Luiz U LU Pham Luu V LV Ladenheim Ellen E EE Spencer Richard R Mendelowitz David D Schwartz Alan R AR Polotsky Vsevolod Y VY

Scientific reports 20170310

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 th ...[more]

PMID: 28281681

Similar Datasets

Project description:ImportanceRecent retrospective hypoglossal nerve stimulation (HGNS) outcomes data suggest that patients with low therapeutic positive airway pressure (PAP) levels achieve greater success than patients with high therapeutic PAP levels.ObjectiveTo examine the use of therapeutic nasal PAP levels at the soft palate in predicting the outcomes of HGNS for patients with obstructive sleep apnea.Design, setting, and participantsThis prospective cohort study used drug-induced sleep endoscopy (DISE) to evaluate the predictive capacity of therapeutic PAP levels in HGNS outcomes. In an academic sleep surgery center, 27 consecutive patients with obstructive sleep apnea who underwent DISE before implantation of an HGNS device were evaluated. The study was conducted from May 1, 2018, to June 26, 2019.ExposuresPositive airway pressure delivered through a nasal mask during DISE.Main outcomes and measuresImprovement in apnea-hypopnea index as measured from full-night preoperative and postoperative efficacy studies.ResultsTwenty-seven patients met all inclusion criteria. The mean (SD) age was 62.0 (14.4) years, 14 participants were men (51.9%), and mean body mass index was 28.1 (4.0). Responders to HGNS therapy (n = 18) had significantly lower mean (SD) palatal opening pressure compared with nonresponders (n = 9) (5.0 [2.8] vs 9.2 [3.7] cm H2O, respectively; mean difference, -4.2; 95% CI, -6.8 to -1.6 cm H2O). After adjusting for age, sex, and body mass index, the mean palatal opening pressure value for the responders remained 3.5 cm H2O lower (95% CI, -6.7 to -0.4 cm H2O) than that of nonresponders. A palatal opening pressure cutoff level less than 8 cm H2O demonstrated a positive predictive value of 82.4%; sensitivity, 77.8%; and specificity, 66.7%.Conclusions and relevanceIn this small prospective cohort study, therapeutic nasal PAP levels during DISE differed significantly between responder and nonresponders to HGNS. Because DISE represents a mandatory, relatively standardized diagnostic tool for HGNS candidacy, the use of therapeutic nasal PAP through DISE can be broadly implemented and studied across multiple centers to possibly improve patient selection for HGNS.

Dataset Information

Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency.

Publications

Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets