Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

Stettner, Georg M.; Fenik, Victor B.; Kubin, Leszek

doi:10.1152/japplphysiol.00697.2011

Cited by 16 publications

(18 citation statements)

References 57 publications

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“…Interestingly, locomotor activity of Wistar-Kyoto rats was increased for at least 3 days after 35 days of exposure to CIH despite the absence of evidence for an increased NE or 5-HT metabolism in the brain (303). This is similar to the increased activation of XII motoneurons by endogenous NE despite the absence of evidence for increased baseline activity of brainstem NE neurons (517, 519). …”

Section: Neural Control Of the Upper Airway In Sleep-disordered Breatsupporting

confidence: 65%

“…To test this, rats were subjected to 35 days of CIH or sham treatment and then the effects of α 1 -adrenergic receptor agonists and antagonists injected into the XII nucleus on XII nerve activity were measured under urethane anesthesia (517). While the magnitude of the excitatory effect of the agonist (phenylephrine) did not differ between the CIH- and sham-treated rats, microinjections of the antagonist (prazosin) caused larger decrements of spontaneous XII nerve activity in CIH animals (Fig.…”

Section: Neural Control Of the Upper Airway In Sleep-disordered Breatmentioning

confidence: 99%

“…It is possible that qualitatively different effects of CIH have different thresholds, but there is currently no common scale with which one can compare the levels of CIH applied in different experimental settings. As an example, data from what seems to be a moderate level of CIH yielded results indicative of an enhancement of endogenous excitatory drive to XII motoneurons mediated by NE (443, 517). However, in other CIH studies in mice, a more prolonged and possibly more severe CIH elicited evidence of injury in wake-active brain neurons, including the LC but not other NE groups (618), sleepiness that persisted after termination of hypoxia (562), and reduced ability of glutamate and 5-HT to activate XII motoneurons (565).…”

Section: Neural Control Of the Upper Airway In Sleep-disordered Breatmentioning

confidence: 99%

“…(Panels D and E modified from Fig. 3 in Ref. 517 and republished with permission from the American Physiological Society.…”

Section: Figurementioning

confidence: 99%

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Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Kubin

2016

Comprehensive Physiology

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Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA.

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Section: Neural Control Of the Upper Airway In Sleep-disordered Breatsupporting

confidence: 65%

Section: Neural Control Of the Upper Airway In Sleep-disordered Breatmentioning

confidence: 99%

Section: Neural Control Of the Upper Airway In Sleep-disordered Breatmentioning

confidence: 99%

“…(Panels D and E modified from Fig. 3 in Ref. 517 and republished with permission from the American Physiological Society.…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Kubin

2016

Comprehensive Physiology

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“…To test whether this is the case, in urethane-anesthetized, paralyzed, and artificially ventilated rats previously subjected to CIH or sham treatment for 35 days, we tested the effects of α 1 -adrenoreceptor agonists and antagonists injected into the XII nucleus on spontaneous XII nerve activity (Stettner et al, 2012). Microinjections of the α 1 -adrenoceptor agonist, phenylephrine into the XII nucleus predictably increased XII nerve activity.…”

Section: Na Control Of the Upper Airway Following Exposure To Chronmentioning

confidence: 99%

Sleep–Wake Control of the Upper Airway by Noradrenergic Neurons, with and without Intermittent Hypoxia

Kubin

2014

Progress in Brain Research

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Hypoglossal (XII) motoneurons innervate muscles of the tongue whose tonic and inspiratory modulated activity protects the upper airway from collapse in patients affected by the obstructive sleep apnea (OSA) syndrome. Both norepinephrine and serotonin provide wakefulness-related excitatory drives that maintain activity in XII motoneurons, with the noradrenergic system playing a particularly prominent role in rats. When noradrenergic and serotonergic drives are antagonized, no further decline of XII nerve activity occurs during pharmacologically induced rapid eye movement (REM) sleep-like state. This is the best evidence to date that, at least in this model, the entire REM sleep-related decline of upper airway muscle tone results from withdrawal of these two excitatory inputs. A major component of noradrenergic input to XII motoneurons originates from pontine noradrenergic neurons that have state-dependent patterns of activity, maximal during wakefulness, and minimal, or absent during REM sleep. Our data suggest that not all ventrolateral medullary catecholaminergic neurons follow this pattern, with adrenergic C1 neurons probably increasing their activity during REM sleep. When rats are subjected to chronic-intermittent hypoxia, noradrenergic drive to XII motoneurons is increased by mechanisms that include sprouting of noradrenergic terminals in the XII nucleus, and increased expression of α1-adrenoceptors; an outcome that may underlie the elevated baseline activity of upper airway muscles during wakefulness in OSA patients.

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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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Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

Cited by 16 publications

References 57 publications

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Sleep–Wake Control of the Upper Airway by Noradrenergic Neurons, with and without Intermittent Hypoxia

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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