Respiratory physiology & neurobiology · 2014
Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse.
СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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Moore Michael W, Akladious Afaf, Hu Yufen, Azzam Sausan, Feng Pingfu, Strohl Kingman P
Аннотация
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.
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.
Предметные рубрики MeSH
AnimalsApneaBrainCatheters, IndwellingCentral Nervous System AgentsDisease Models, AnimalElectrodes, ImplantedElectroencephalographyFemaleIsoquinolinesMaleMice, Inbred C57BLOrexin Receptor AntagonistsOrexin ReceptorsPlethysmographyPolysomnographyPyridinesRandom AllocationSex CharacteristicsSleepWakefulness