α2-Adrenergic blockade rescues hypoglossal motor defense against obstructive sleep apnea

Song, Gang; Poon, Chi‐Sang

doi:10.1172/jci.insight.91456

Cited by 17 publications

(18 citation statements)

References 67 publications

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“…). Moreover, recent animal data have shown that the administration of the α2‐antagonist yohimbine greatly increased the genioglossus activity after the induction of repeated upper airway obstruction during sleep, suggesting that it may be possible to pharmacologically enhance genioglossus‐specific forms of neural memory (Song & Poon, ).…”

Section: Discussionmentioning

confidence: 99%

“…[Colour figure can be viewed at wileyonlinelibrary.com] recent animal data have shown that the administration of the α2-antagonist yohimbine greatly increased the genioglossus activity after the induction of repeated upper airway obstruction during sleep, suggesting that it may be possible to pharmacologically enhance genioglossus-specific forms of neural memory (Song & Poon, 2017). The mechanisms responsible for the link between increased genioglossus memory and SWS are still largely unknown.…”

Section: Example Of Ventilatory Drive Tonic and Phasic Genioglossumentioning

confidence: 99%

“…short‐term potentiation, after discharge, long‐term facilitation of hypoglossal motor nucleus) as potential compensatory mechanisms (Mateika & Syed, ; Younes et al . ; Song & Poon, ).…”

Section: Introductionmentioning

confidence: 98%

“…Recent animal and human studies identified some forms of vagally-mediated neural memory (i.e. short-term potentiation, after discharge, long-term facilitation of hypoglossal motor nucleus) as potential compensatory mechanisms (Mateika & Syed, 2013;Younes et al 2014;Song & Poon, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

Taranto‐Montemurro

Sands

Grace

et al. 2018

The Journal of Physiology

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Several studies have shown that obstructive sleep apnoea (OSA) improves during slow wave sleep (SWS) for reasons that remain unclear. Recent studies have identified forms of neural memory such as short-term potentiation or after-discharge that can occur in response to upper airway obstruction. Neural memory may play a role in the development of stable breathing during SWS by increasing upper airway muscles activity in this sleep stage. We hypothesize that the after-discharge of the genioglossus muscle following upper airway obstruction is enhanced during SWS compared to non-rapid eye movement stage 2 (N2). During sleep, we performed five-breath drops in continuous positive airway pressure (CPAP-drop) to simulate obstructive events and reflexively activate the genioglossus. Immediately afterwards, CPAP was returned to an optimal level. Once the post-drop ventilation returned to eupnoea, the genioglossus after-discharge was measured as the time it took for genioglossus activity to return to baseline levels. In total, 171 CPAP-drops were analysed from a group of 16 healthy subjects and 19 OSA patients. A mixed-model analysis showed that after-discharge duration during SWS was 208% (95% confidence interval = 112% to 387%, P = 0.022) greater than during N2 after adjusting for covariates (ventilatory drive, CPAP levels). There was also a non-significant trend for a -35% reduction in after-discharge duration following an arousal vs. no-arousal from sleep (95% confidence interval = -59.5% to 5%, P = 0.08). Genioglossus after-discharge is two-fold greater in SWS vs. N2, which could partly explain the breathing stabilization described in OSA patients during this sleep stage.

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Section: Discussionmentioning

confidence: 99%

Section: Example Of Ventilatory Drive Tonic and Phasic Genioglossumentioning

confidence: 99%

“…short‐term potentiation, after discharge, long‐term facilitation of hypoglossal motor nucleus) as potential compensatory mechanisms (Mateika & Syed, ; Younes et al . ; Song & Poon, ).…”

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

Taranto‐Montemurro

Sands

Grace

et al. 2018

The Journal of Physiology

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“…The blockade of GIRK channels in the hypoglossal motor pool with barium augmented tonic and respiratory-related GG activity in rats, reversing the upper airway hypotonia during NREM and REM sleep [66] (Table 1). Song and Poon [67] provided another line of evidence that noradrenergic stimulation plays an important role in GG muscle control. The investigators used yohimbine, an antagonist of presynaptic α2-adrenerereceptor (i.e., a noradrenergic agonist).…”

Section: Animal Models Of Neuromuscular Response: Emg Outcomesmentioning

confidence: 99%

The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea

Kim

Freire

Curado

et al. 2019

JCM

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Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of the pharynx, but it may not be sufficient for OSA development. Non-anatomical traits, including (1) a compromised neuromuscular response of the upper airway to obstruction, (2) an unstable respiratory control (high loop gain), and (3) a low arousal threshold, predict the development of OSA in association with anatomical abnormalities. Current therapies for OSA, such as continuous positive airway pressure (CPAP) and oral appliances, have poor adherence or variable efficacy among patients. The search for novel therapeutic approaches for OSA, including pharmacological agents, has been pursued over the past years. New insights into OSA pharmacotherapy have been provided by preclinical studies, which highlight the importance of appropriate use of animal models of OSA, their applicability, and limitations. In the present review, we discuss potential pharmacological targets for OSA discovered using animal models.

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Transient upregulation of TASK‐1 expression in the hypoglossal nucleus during chronic intermittent hypoxia is reduced by serotonin 2A receptor antagonist

Wang

Jin

et al. 2019

Journal Cellular Physiology

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Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK‐related acid‐sensitive K+ channel‐1 (TASK‐1) could be inhibited by 5‐HT. This study aimed to investigate if TASK‐1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5‐HT2A receptors antagonist. Two hundred twenty‐eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5‐HT 2A receptor antagonist (MDL‐100907) microinjected into the hypoglossal nucleus. The expression of 5‐HT and TASK‐1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5‐HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day ( p < 0.05). Compared with the NO group, the MOD and gene expression of TASK‐1 in the CIH group was significantly increased on the 7th and 14th day ( p < 0.05), then normalized on the 21st day. The TASK‐1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day ( p < 0.05). The CIH‐induced transiently upregulation of the TASK‐1 expression in the hypoglossal nucleus could be reversed by 5‐HT 2A receptor antagonist, indicating that the modulation of the TASK‐1 expression in response to CIH involves 5‐HT and 5‐HT 2A receptors, and this CIH effect might be 5‐HT 2A receptor‐dependent.

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α2-Adrenergic blockade rescues hypoglossal motor defense against obstructive sleep apnea

Cited by 17 publications

References 67 publications

Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea

Transient upregulation of TASK‐1 expression in the hypoglossal nucleus during chronic intermittent hypoxia is reduced by serotonin 2A receptor antagonist

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