Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles

Rukhadze, Irma; Carballo, Nancy J.; Bandaru, Sathyajit S.; Malhotra, Atul; Fuller, Patrick M.; Fenik, Victor B.

doi:10.1016/j.resp.2017.07.001

Cited by 14 publications

(16 citation statements)

References 80 publications

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“…Neurons in the pre-Botzinger complex, which are responsible for generating respiratory rhythms, experience vesicle accumulation in the somas of Gaa −/− but not WT mice [44]. Neurons in the A1/C1 group, which are speculated to modulate and activate breathing, especially during hypoxia, also have abnormal morphology and vesicle accumulation in Gaa −/− but not WT mice [44,68,69].…”

Section: Additional Neural Control Centersmentioning

confidence: 99%

The Respiratory Phenotype of Pompe Disease Mouse Models

Fusco

McCall

Dhindsa

et al. 2020

IJMS

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Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA), a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease mouse models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts that characterize the respiratory phenotype of Pompe mouse models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease mouse models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, higher-order respiratory control centers, phrenic and hypoglossal motor nuclei, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

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Section: Additional Neural Control Centersmentioning

confidence: 99%

The Respiratory Phenotype of Pompe Disease Mouse Models

Fusco

McCall

Dhindsa

et al. 2020

IJMS

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“…Neurons in the pre-Botzinger complex, which are responsible for generating respiratory rhythms, experience vesicle accumulation in the somas of Gaa -/-but not WT mice [41]. Neurons in the A1/C1 group, which are speculated to modulate and activate breathing especially during hypoxia, also have abnormal morphology and vesicle accumulation in Gaa -/-but not WT mice [41,64,65].…”

Section: Additional Neural Control Centersmentioning

confidence: 99%

The Respiratory Phenotype of Pompe Disease Rodent Models

Fusco¹,

McCall²,

Dhindsa³

et al. 2020

Preprint

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Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

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“…However theoretically, there is a possibility that the release of noradrenaline from A1 terminals within the hypoglossal nucleus is modulated through some sleep-specific presynaptic inhibitory mechanisms, similar to the discovered earlier, presynaptic cholinergic control of glutamate release to hypoglossal motoneurons ( 62 ). To this end, we recently tested the role of medullary A1/C1 neurons in control of the activity of genioglossus muscle using the “designer receptor exclusively activated by a designer drug” (DREADD) technique ( 77 ). A Cre-dependent viral vector hSyn-Dio-hM4Di-mCherry-AAV10 was microinjected into the A1/C1 region, which resulted in the expression of inhibitory receptors in the A1/C1 neurons in behaving dopamine β-hydroxylase (DBH)-cre mice, in which the Cre-recombinase is expressed in all catecholaminergic neurons.…”

Section: Neurotransmitters Implicated In the Control Of Hypoglossal Mmentioning

confidence: 99%

“…This suggested that A1/C1 neurons provide a net excitatory effect on the activity of upper airway muscles. However, the relative effect of CNO on the genioglossus activity was similar during both wakefulness and NREM sleep suggesting that A1/C1 neurons do not contribute to depression of genioglossus activity during transition from wakefulness to NREM sleep ( 77 ).…”

Section: Neurotransmitters Implicated In the Control Of Hypoglossal Mmentioning

confidence: 99%

Neuroanatomical Basis of State-Dependent Activity of Upper Airway Muscles

Rukhadze

Fenik

2018

Front. Neurol.

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Obstructive Sleep Apnea (OSA) is a common sleep-related respiratory disorder that is associated with cognitive, cardiovascular, and metabolic morbidities. The major cause of OSA is the sleep-related reduction of upper airway muscle tone that leads to airway obstructions in individuals with anatomically narrow upper airway. This reduction is mainly due to the suppressant effect of sleep on hypoglossal motoneurons that innervate upper airway muscles. The hypoglossal motoneurons have state-dependent activity, which is decreased during the transition from wakefulness to non-rapid eye movement sleep and is further suppressed during rapid eye movement sleep. Multiple neurotransmitters and their receptors have been implicated in the control of hypoglossal motoneuron activity across the sleep-wake states. However, to date, the results of the rigorous testing show that withdrawal of noradrenergic excitation and cholinergic inhibition essentially contribute to the depression of hypoglossal motoneuron activity during sleep. The present review will focus on origins of noradrenergic and cholinergic innervation of hypoglossal motoneurons and the functional role of these neurons in the state-dependent activity of hypoglossal motoneurons.

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Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles

Cited by 14 publications

References 80 publications

The Respiratory Phenotype of Pompe Disease Mouse Models

The Respiratory Phenotype of Pompe Disease Mouse Models

The Respiratory Phenotype of Pompe Disease Rodent Models

Neuroanatomical Basis of State-Dependent Activity of Upper Airway Muscles

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