scholarly journals The Effect of DREADD Activation of Leptin Receptor Positive Neurons in the Nucleus of the Solitary Tract on Sleep Disordered Breathing

2021 ◽  
Vol 22 (13) ◽  
pp. 6742
Author(s):  
Mateus R. Amorim ◽  
Olga Dergacheva ◽  
Thomaz Fleury-Curado ◽  
Huy Pho ◽  
Carla Freire ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Muscle Tone ◽  
Upper Airway ◽  
Designer Drugs ◽  
Solitary Tract ◽  
Airway Patency ◽  
Tongue Muscle ◽  
Obstructive Sleep ◽  
Respiratory Stimulant ◽  
Upper Airway Muscles

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway due to the loss of upper airway muscle tone during sleep. OSA is highly prevalent, especially in obesity. There is no pharmacotherapy for OSA. Previous studies have demonstrated the role of leptin, an adipose-tissue-produced hormone, as a potent respiratory stimulant. Leptin signaling via a long functional isoform of leptin receptor, LEPRb, in the nucleus of the solitary tract (NTS), has been implicated in control of breathing. We hypothesized that leptin acts on LEPRb positive neurons in the NTS to increase ventilation and maintain upper airway patency during sleep in obese mice. We expressed designer receptors exclusively activated by designer drugs (DREADD) selectively in the LEPRb positive neurons of the NTS of Leprb-Cre-GFP mice with diet-induced obesity (DIO) and examined the effect of DREADD ligand, J60, on tongue muscle activity and breathing during sleep. J60 was a potent activator of LEPRb positive NTS neurons, but did not stimulate breathing or upper airway muscles during NREM and REM sleep. We conclude that, in DIO mice, the stimulating effects of leptin on breathing during sleep are independent of LEPRb signaling in the NTS.

Control of respiratory activity of the genioglossus muscle in micrognathic infants

1986 ◽  
Vol 61 (4) ◽  
pp. 1523-1533 ◽  
Author(s):  
J. L. Roberts ◽  
W. R. Reed ◽  
O. P. Mathew ◽  
B. T. Thach
Keyword(s):  
Upper Airway ◽  
Esophageal Pressure ◽  
Progressive Increase ◽  
Emg Activity ◽  
Nasal Breathing ◽  
Airway Patency ◽  
Tongue Muscle ◽  
Airway Occlusion ◽  
Pharyngeal Airway ◽  
Obstructive Sleep

The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.

scholarly journals GABA and glycine neurons from the ventral medullary region inhibit hypoglossal motoneurons

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Olga Dergacheva ◽  
Thomaz Fleury-Curado ◽  
Vsevolod Y Polotsky ◽  
Matthew Kay ◽  
Vivek Jain ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Muscle Tone ◽  
Upper Airway ◽  
Emg Activity ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Obstructive Sleep ◽  
Tongue Muscles

Abstract Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive sleep-related losses of upper airway patency that occur most frequently during rapid eye movement (REM) sleep. Hypoglossal motoneurons play a key role in regulating upper airway muscle tone and patency during sleep. REM sleep activates GABA and glycine neurons in the ventral medulla (VM) to induce cortical desynchronization and skeletal muscle atonia during REM sleep; however, the role of this brain region in modulating hypoglossal motor activity is unknown. We combined optogenetic and chemogenetic approaches with in-vitro and in-vivo electrophysiology, respectfully, in GAD2-Cre mice of both sexes to test the hypothesis that VM GABA/glycine neurons control the activity of hypoglossal motoneurons and tongue muscles. Here, we show that there is a pathway originating from GABA/glycine neurons in the VM that monosynaptically inhibits brainstem hypoglossal motoneurons innervating both tongue protruder genioglossus (GMNs) and retractor (RMNs) muscles. Optogenetic activation of ChR2-expressing fibers induced a greater postsynaptic inhibition in RMNs than in GMNs. In-vivo chemogenetic activation of VM GABA/glycine neurons produced an inhibitory effect on tongue electromyographic (EMG) activity, decreasing both the amplitude and duration of inspiratory-related EMG bursts without any change in respiratory rate. These results indicate that activation of GABA/glycine neurons from the VM inhibits tongue muscles via a direct pathway to both GMNs and RMNs. This inhibition may play a role in REM sleep associated upper airway obstructions that occur in patients with OSA.

Obstructive Sleep Apnea: Epidemiology, Causes, and Consequences

2020 ◽  
Author(s):  
Diane C Lim ◽  
Richard J Schwab
Keyword(s):  
Risk Factors ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cushing Syndrome ◽  
Upper Airway ◽  
Fat Distribution ◽  
Epidemiologic Studies ◽  
Obstructive Sleep ◽  
Upper Airway Muscles ◽  
Underlying Diseases

As part one of the three chapters on sleep-disordered breathing, this chapter reviews obstructive sleep apnea (OSA) epidemiology, causes, and consequences. When comparing OSA prevalence between 1988 to 1994 and 2007 to 2010, we observe that OSA is rapidly on the rise, paralleling increasing rates in obesity. Global epidemiologic studies indicate that there are differences specific to ethnicity with Asians presenting with OSA at a lower body mass index than Caucasians. We have learned that structural and physiologic factors increase the risk of OSA and both can be influenced by genetics. Structural risk factors include craniofacial bony restriction, changes in fat distribution, and the size of the upper airway muscles. Physiologic risk factors include airway collapsibility, loop gain, pharyngeal muscle responsiveness, and arousal threshold. The consequences of OSA include daytime sleepiness and exacerbation of many underlying diseases. OSA has been associated with cardiovascular diseases including hypertension, coronary heart disease, stroke, atrial fibrillation, and other cardiac arrhythmias; pulmonary hypertension; metabolic disorders such as type 2 diabetes, hypothyroidism, acromegaly, Cushing syndrome, and polycystic ovarian syndrome; mild cognitive impairment or dementia; and cancer. This review contains 4 figures, 1 table and 48 references. Key Words: cardiac consequences, craniofacial bony restriction, epidemiology, fat distribution, metabolic disease, neurodegeneration, obesity, obstructive sleep apnea

Mass loading of the upper airway extraluminal tissue space in rabbits: effects on tissue pressure and pharyngeal airway lumen geometry

2009 ◽  
Vol 106 (3) ◽  
pp. 887-892 ◽  
Author(s):  
Kristina Kairaitis ◽  
Lauren Howitt ◽  
John R. Wheatley ◽  
Terence C. Amis
Keyword(s):  
Pressure Transducer ◽  
Tissue Expander ◽  
Upper Airway ◽  
Fat Pad ◽  
Pharyngeal Wall ◽  
Airway Patency ◽  
Pharyngeal Airway ◽  
Obstructive Sleep ◽  
Tracheal Pressure ◽  
Tissue Space

Lateral pharyngeal fat pad compression of the upper airway (UA) wall is thought to influence UA size in patients with obstructive sleep apnea. We examined interactions between acute mass/volume loading of the UA extra-luminal tissue space and UA patency. We studied 12 supine, anesthetized, spontaneously breathing, head position-controlled (50°), New Zealand White rabbits. Submucosal extraluminal tissue pressures (ETP) in the anterolateral (ETPlat) and anterior (ETPant) pharyngeal wall were monitored with surgically inserted pressure transducer-tipped catheters (Millar). Tracheal pressure (Ptr) and airflow (V̇) were measured via a pneumotachograph and pressure transducer inserted in series into the intact trachea, with hypopharyngeal cross-sectional area (CSA) measured via computed tomography, while graded saline inflation (0–1.5ml) of a compliant tissue expander balloon in the anterolateral subcutaneous tissue was performed. Inspiratory UA resistance (Rua) at 20 ml/s was calculated from a power function fitted to Ptr vs. V̇ data. Graded expansion of the anterolateral balloon increased ETPlat from 2.3 ± 0.5 cmH2O ( n = 11, mean ± SEM) to 5.0 ± 1.1 cmH2O at 1.5-ml inflation ( P < 0.05; ANOVA). However, ETPant was unchanged from 0.5 ± 0.5 cmH2O ( n = 9; P = 0.17). Concurrently, Rua increased to 119 ± 4.2% of baseline value ( n = 12; P < 0.001) associated with a significant reduction in CSA between 10 and 70% of airway length to a minimum of 82.2 ± 4.4% of baseline CSA at 40% of airway length ( P < 0.05). We conclude that anterolateral loading of the upper airway extraluminal tissue space decreases upper airway patency via an increase in ETPlat, but not ETPant. Lateral pharyngeal fat pad size may influence UA patency via increased tissue volume and pressure causing UA wall compression.

Mouth and nose resistance in newborn kittens and puppies

1981 ◽  
Vol 51 (3) ◽  
pp. 641-645 ◽  
Author(s):  
J. P. Mortola ◽  
J. T. Fisher
Keyword(s):  
Mechanical Properties ◽  
Airway Obstruction ◽  
Flow Rate ◽  
Muscle Tone ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Upper Airways ◽  
Airway Patency ◽  
The Difference ◽  
Adult Cats

Newborn mammals, including infants, have difficulties in mouth breathing when the nasal passages are occluded. In this study we examined the possibility that differences in the passive mechanical properties of the upper airways could fully explain this behavior. Steady inspiratory flows through the upper airways in anesthetized supine newborn kittens and puppies resulted in upper airway obstruction, even at flows less than those occurring during resting breathing, suggesting that in the unanesthetized condition muscle tone plays an important role in maintaining upper airway patency. Mouth (Rm) and nose (Rn) resistances have been measured during steady expiratory flows with nostrils closed and mouth passively open or nostrils open and mouth closed. In all the newborns, Rn was substantially smaller than Rm. In contrast, the Rn/Rm in adult dogs is greater than unity. In adult cats Rn/Rm is above or below unity depending upon the flow rate, but the ratio is always larger than in newborn kittens. The difference between newborns and adults is entirely due to the small Rn of the newborn, as Rm is not greater in the newborn than in the adult. We conclude that the obligatory nose breathing behavior of newborns is not fully explained by the passive mechanical properties of the upper airways.

Modulation of the extrinsic tongue muscle activity in response to bronchopulmonary C-fiber activation following midcervical contusion in the rat

2020 ◽  
Vol 128 (5) ◽  
pp. 1130-1145
Author(s):  
Hsiao-Sen Chang ◽  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Muscle Activity ◽  
Cervical Spinal Cord ◽  
Upper Airway ◽  
Airway Patency ◽  
Tongue Muscle ◽  
Cord Injury ◽  
Burst Amplitude ◽  
C Fiber ◽  
Spinal Cord Contusion

Tongue muscle activity plays an important role in the regulation of upper airway patency. This study aimed to investigate the respiratory activity of the extrinsic tongue muscle in response to capsaicin-induced bronchopulmonary C-fiber activation following cervical spinal cord contusion. Midcervical spinal-contused animals exhibited a greater baseline preinspiratory burst amplitude of the extrinsic tongue muscle and were resistant to inhaled capsaicin-induced reduction of respiratory tongue muscle activity at the acute injured stage. However, inhalation of capsaicin caused a more severe attenuation of preinspiratory activity of the extrinsic tongue muscle at the chronic injured stage. These results suggest that the upper airway may be predisposed to collapse in response to bronchopulmonary C-fiber activation following chronic cervical spinal cord injury.

Interacting effects of genioglossus stimulation and mandibular advancement in sleep apnea

2009 ◽  
Vol 106 (5) ◽  
pp. 1668-1673 ◽  
Author(s):  
Ron Oliven ◽  
Naveh Tov ◽  
Majed Odeh ◽  
Luis Gaitini ◽  
Uri Steinfeld ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Airway Pressure ◽  
Upper Airway ◽  
Combined Effect ◽  
Mandibular Advancement ◽  
Cross Sectional ◽  
Airway Patency ◽  
Obstructive Sleep ◽  
Critical Closing Pressure ◽  
Stimulation Of

Both mandibular advancement (MA) and stimulation of the genioglossus (GG) have been shown to improve upper airway patency, but neither one achieves the effect of continuous positive airway pressure (CPAP) treatment. In the present study we assessed the combined effect of MA and GG stimulation on the relaxed pharynx in patients with obstructive sleep apnea (OSA). We evaluated responses of upper airway pressure-flow relationships and endoscopically determined pharyngeal cross-sectional area to MA and electrical stimulation of the GG in 14 propofol-anesthetized OSA patients. Measurements were undertaken at multiple levels of CPAP, enabling calculation of the critical closing pressure (Pcrit), upstream resistance (Rus), and pharyngeal compliance. GG stimulation, MA, and the combination of both shifted the pressure:flow relationships toward higher flow levels, resulting in progressively lower Pcrit (from baseline of 2.9 ± 2.2 to 0.9 ± 2.5, −1.4 ± 2.9, and −4.2 ± 3.3 cmH2O, respectively), without significant change in Rus. ΔPcrit during GG stimulation was significantly larger during MA than under baseline conditions (−2.8 ± 1.4 vs. −2.0 ± 1.4 cmH2O, P = 0.011). Combining the effect of GG stimulation with MA lowered Pcrit below 0 in all patients and restored pharyngeal patency to a level that enabled flow above the hypopnea level in 10/14 of the patients. Velopharyngeal compliance was not affected by either manipulation. We conclude that the combined effect of MA and GG stimulation is additive and may act in synergy, preventing substantial flow limitation of the relaxed pharynx in most OSA patients.

Sign in / Sign up

Export Citation Format

Share Document