5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats

Sood, Sandeep; Liu, Xia; Liu, Hattie; Nolan, P.; Horner, Richard L.

doi:10.1016/j.resp.2003.07.001

Cited by 54 publications

(44 citation statements)

References 52 publications

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“…Zhong et al concluded that intracerebroventricular injection of 5-HT or 5-HT 2A/2C agonists can increase genioglossus activity in rats [8]. Sood and his colleagues further observed that genioglossus activity was increased by 5-HT at the hypoglossal motor nucleus in anesthetized rats [9]. Raphe 5-HT neurons, as respiratory premotor neurons, are subdivided into two main groups.…”

Section: Introductionmentioning

confidence: 99%

Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats

Wang

Sun

et al. 2014

Respir Res

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Background Genioglossus activity is greater during wakefulness but decreases to a weaker state during sleep in obstructive sleep apnea syndrome (OSAS) patients, compared to healthy subjects. Previous studies suggested that the corticomotor control of the genioglossus was modified in OSAS patients. Intermittent hypoxia (IH), the typical pathophysiological change in OSAS, can induce genioglossus facilitation. The serotonergic neurons of the raphe dorsal (DRN) and magnus nuclei (RMg) are responsive to hypoxia and play important roles in the control of the genioglossus. However, it remains unknown whether DRN and RMg serotonergic neurons are responsible for the facilitated corticomotor activity of the genioglossus during IH. This study explored the influence of IH on the corticomotor activity of the genioglossus by transcranial magnetic stimulation (TMS), and the role of DRN and RMg serotonergic neurons in this effect. Methods Rats were exposed to IH and divided into two groups. In one group, anti-SERT-SAP was microinjected into the DRN and RMg respectively to kill serotonergic neurons. In the other group, artificial cerebrospinal fluid (ACSF) was injected. Comparisons were conducted between the two groups during four weeks of IH and four weeks after IH. Results Compared to the corresponding ACSF-injected group, the DRN lesion group and RMg lesion group showed longer TMS latencies and lower amplitudes during IH from the 1 st to the 28 th day. After 28 days of IH, longer latencies and lower amplitudes were seen only in the DRN lesion group. Conclusion These results indicate that DRN and RMg serotonergic neurons play different roles in the facilitation of genioglossus corticomotor activity induced by IH.

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Section: Introductionmentioning

confidence: 99%

Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats

Wang

Sun

et al. 2014

Respir Res

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“…Withdrawal of endogenous serotonin at the hypoglossal nucleus was long thought to be the primary mechanism underlying decreased pharyngeal muscle activity during sleep (6). However, the studies implicating serotonin were conducted in vagotomized animals (7). It is now known that vagal afferents inhibit serotonin at the hypoglossal nucleus and thus vagotomy will exaggerate the influence of endogenous serotonin.…”

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confidence: 99%

Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects

Taranto‐Montemurro

Edwards

Sands

et al. 2016

Am J Respir Crit Care Med

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Rationale: Obstructive sleep apnea is a state-dependent disease. One of the key factors that triggers upper airway collapse is decreased pharyngeal dilator muscle activity during sleep. To date, there have not been effective methods to reverse pharyngeal hypotonia pharmacologically in sleeping humans.Objectives: We tested the hypothesis that administration of desipramine 200 mg prevents the state-related reduction in genioglossus activity that occurs during sleep and thereby decreases pharyngeal collapsibility.Methods: We conducted a placebo-controlled, double-blind, crossover trial with 10 healthy participants. Participants received active treatment or placebo in randomized order 2 hours before sleep in the physiology laboratory.Measurements and Main Results: Genioglossus activity during wakefulness and sleep, genioglossus muscle responsiveness to negative epiglottic pressure, and upper airway collapsibility during passive and active conditions were compared between on-and off-drug states. Desipramine abolished the normal reduction of genioglossus activity from wakefulness to non-REM sleep that occurred on the placebo night. Specifically, tonic (median, 96% [86-120] vs. 75% wakefulness; P = 0.01) but not phasic genioglossus activity was higher with desipramine compared with placebo. Upper airway collapsibility was also reduced with desipramine compared with placebo Conclusions: Desipramine reduces the state-related drop in tonic genioglossus muscle activity that occurs from wakefulness to non-REM sleep and reduces airway collapsibility. These data provide a rationale for a new pharmacologic therapy for obstructive sleep apnea.Clinical trial registered with www.clinicaltrials.gov (NCT02428478).

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“…Studies in anesthetized or decerebrate animals with the vagus nerves cut have shown that 5-HT receptor antagonism at the hypoglossal motor pool causes a decrease in spontaneous GG activity, confirming the presence of an endogenously active 5-HT tone (67,122,134,269,270,522,524,620,641). Although the GG muscle is still able to respond to CO 2 stimulation, however, after 5-HT receptor antagonism, the magnitude of the increase in GG activity elicited by CO 2 is significantly reduced (522), consistent with a role for 5-HT mechanisms at the hypoglossal motor pool contributing to the full expression of GG muscle responses to CO 2 .…”

Section: Contribution Of Arousal Mechanisms and Sleep-state Dependentmentioning

confidence: 90%

“…Although the GG muscle is still able to respond to CO 2 stimulation, however, after 5-HT receptor antagonism, the magnitude of the increase in GG activity elicited by CO 2 is significantly reduced (522), consistent with a role for 5-HT mechanisms at the hypoglossal motor pool contributing to the full expression of GG muscle responses to CO 2 . However, a review of all the previous studies demonstrating a significant endogenous 5-HT drive to the hypoglossal motor nucleus showed that they were all performed in the presence of vagotomy in anesthetized or decerebrate animals (67,122,134,269,270,522,524,620,641). Importantly, although respiratory-related GG activity is present in both vagotomized and vagus nerve intact animals, vagotomy augments the influence of 5-HT at the hypoglossal motor pool (523,524).…”

Section: Contribution Of Arousal Mechanisms and Sleep-state Dependentmentioning

confidence: 99%

Neural Control of the Upper Airway: Integrative Physiological Mechanisms and Relevance for Sleep Disordered Breathing

Horner

2012

Comprehensive Physiology

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The various neural mechanisms affecting the control of the upper airway muscles are discussed in this review, with particular emphasis on structure-function relationships and integrative physiological motor-control processes. Particular foci of attention include the respiratory function of the upper airway muscles, and the various reflex mechanisms underlying their control, specifically the reflex responses to changes in airway pressure, reflexes from pulmonary receptors, chemoreceptor and baroreceptor reflexes, and postural effects on upper airway motor control. This article also addresses the determinants of upper airway collapsibility and the influence of neural drive to the upper airway muscles, and the influence of common drugs such as ethanol, sedative hypnotics, and opioids on upper airway motor control. In addition to an examination of these basic physiological mechanisms, consideration is given throughout this review as to how these mechanisms relate to integrative function in the intact normal upper airway in wakefulness and sleep, and how they may be involved in the pathogenesis of clinical problems such obstructive sleep apnea hypopnea.

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5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats

Cited by 54 publications

References 52 publications

Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats

Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats

Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects

Neural Control of the Upper Airway: Integrative Physiological Mechanisms and Relevance for Sleep Disordered Breathing

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