Michael W Moore1, Afaf Akladious1, Yufen Hu2, Sausan Azzam3, Pingfu Feng2, Kingman P Strohl4. 1. Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States. 2. Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Neogene Biosciences LLC, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States. 3. Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Case Western Reserve University, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States. 4. Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Case Western Reserve University, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States. Electronic address: kpstrohl@aol.com.
Abstract
BACKGROUND: The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing. METHODS: In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29. RESULTS: A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels. CONCLUSIONS: The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness. Published by Elsevier B.V.
BACKGROUND: The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing. METHODS: In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCSOX2 29. RESULTS: A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels. CONCLUSIONS: The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness. Published by Elsevier B.V.
Authors: M W Moore; S Chai; C B Gillombardo; A Carlo; L M Donovan; N Netzer; K P Strohl Journal: Respir Physiol Neurobiol Date: 2012-05-15 Impact factor: 1.931
Authors: Paulina M Getsy; Jesse Davis; Gregory A Coffee; Walter J May; Lisa A Palmer; Kingman P Strohl; Stephen J Lewis Journal: Respir Physiol Neurobiol Date: 2014-09-19 Impact factor: 1.931
Authors: Paulina M Getsy; Sripriya Sundararajan; Walter J May; Graham C von Schill; Dylan K McLaughlin; Lisa A Palmer; Stephen J Lewis Journal: Sci Rep Date: 2021-10-18 Impact factor: 4.379
Authors: Paulina M Getsy; Sripriya Sundararajan; Walter J May; Graham C von Schill; Dylan K McLaughlin; Lisa A Palmer; Stephen J Lewis Journal: Sci Rep Date: 2021-09-15 Impact factor: 4.379