CNS determinants of sleep-related worsening of airway functions: Implications for nocturnal asthma

Haxhiu, Musa A.; Rust, Cheryl F.; Brooks, Chevon; Kc, Prabha

doi:10.1016/j.resp.2005.07.009

Cited by 11 publications

(8 citation statements)

References 238 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Located bilaterally in the dorsal pons at the floor of the fourth ventricle, the LC contains the largest concentration of catecholamine containing neurons in the central nervous system, exhibits activity that is arousal state-dependent, and modulates sensory information, arousal, feeding, pain processing, and cardiovascular control (8, 16, 67, 110). LC neurons play a role in the development of the respiratory network (94) and can modulate respiratory rhythm (95, 198). CO2 stimulation in vivo induces c-fos expression in the LC (93, 254).…”

Section: The Location Of Central Chemoreceptorsmentioning

confidence: 99%

Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

204

139

View full text Add to dashboard Cite

Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H+ detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H+, serves to detect and integrate information on 1) alveolar ventilation (arterial PCO2), 2) brain blood flow and metabolism and 3) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone) and arousal. In addition, central chemoreception provides a tonic ‘drive’ (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air vs. water breathing, homeothermy, sleep, optimization of the work of breathing with the ‘ideal’ arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function.

show abstract

Section: The Location Of Central Chemoreceptorsmentioning

confidence: 99%

Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

204

139

View full text Add to dashboard Cite

show abstract

“…The critical circuits which regulate these processes include central glutamatergic, GABAergic, noradrenergic and serotonergic pathways controlling cholinergic outflow to the airways (Haxhiu et al, 1987, 1991, 1997, 1998, 2000a, 2000b, 2002, 2003a, 2006). Using neuronal tracing techniques as well as ultrastructural, molecular and physiologic approaches, the central excitatory (Haxhiu et al, 1986, 1987, 1989a, 1997, 1998), as well as inhibitory pathways, and neurotransmitters (Haxhiu et al, 1986, 1998, 2000b, 2002) that are involved in regulating the excitability and firing rate of AVPNs have been determined.…”

Section: Airway-related Vagal Preganglionic Neuronsmentioning

confidence: 99%

“…Immunolabeling studies have demonstrated that 5-HT-immunoreactive fibers exist within the rNA in close proximity to AVPNs (Haxhiu et al, 2006). Similarly, the retrograde transneuronal labeling method showed that AVPNs are innervated by the medullary raphe complex which consists of the raphe magnus, raphe obscurus and raphe pallidus (Haxhiu et al, 1993).…”

Section: Central Innervation Of Avpnsmentioning

confidence: 99%

“…This response was diminished following blockade of serotonin receptors in the rNA by microinjection of methysergide, a non-selective serotonin receptor (mixed 5-HT 1 /5-HT 2 receptor) antagonist (Figure 4). Among the 14 different 5-HT receptor subtypes so far characterized (Martin et al, 1998), the 5-HT 1A receptor is expressed in high density by the AVPNs, and is found on a somatodendritic postsynaptic site (Haxhiu et al, 2006). 5-HT 1A receptors are inhibitory in nature, whereas 5-HT 2 receptors, as found for example in hypoglossal motoneurons, exert stimulatory effects (Haxhiu et al, 1998, Kubin et al, 1992).…”

Section: Central Innervation Of Avpnsmentioning

confidence: 99%

See 1 more Smart Citation

Role of central neurotransmission and chemoreception on airway control

Martin

2010

Respiratory Physiology & Neurobiology

Self Cite

View full text Add to dashboard Cite

This review summarizes work on central neurotransmission, chemoreception and CNS control of cholinergic outflow to the airways. First, we describe the neural transmission of bronchoconstrictive signals from airway afferents to the airway-related vagal preganglionic neurons (AVPNs) via the nucleus of the solitary tract (nTS) and, second, we characterize evidence for a modulatory effect of excitatory glutamatergic, and inhibitory GABAergic, noradrenergic and serotonergic pathways on AVPN output. Excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second order neurons within the nTS, via a glutamate-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor signaling pathway. These nTS neurons, using the same neurotransmitter-receptor unit, transmit information to the AVPNs, which in turn convey the central command through descending fibers and airway intramural ganglia to airway smooth muscle, submucosal secretory glands, and the vasculature. The strength and duration of this reflex-induced bronchoconstriction is modulated by GABAergic-inhibitory inputs. In addition, central noradrenergic and serotonergic inhibitory pathways appear to participate in the regulation of cholinergic drive to the tracheobronchial system. Down-regulation of these inhibitory influences results in a shift from inhibitory to excitatory drive, which may lead to increased excitability of AVPNs, heightened airway responsiveness, greater cholinergic outflow to the airways and consequently bronchoconstriction. In summary, centrally coordinated control of airway tone and respiratory drive serve to optimize gas exchange and work of breathing under normal homeostatic conditions. Greater understanding of this process should enhance our understanding of its disruption under pathophysiologic states.

show abstract

“…Moreover, in a ferret model of allergic asthma, the expression of ␣ 2Aadrenoceptors is downregulated in the eNA, and local microperfusion of an ␣ 2A -adrenoceptor agonist blunts the decrease in airway muscle tension (34). Consequently, attenuated ␣ 2 -adrenergic inhibition of the AVPNs, which might become worse during sleep due to reduced or silenced pontine noradrenergic activity, is suggested to be involved in not just the pathogenesis of asthma, but also in its sleep-related worsening (15,34).…”

mentioning

confidence: 99%

Activation of α₁-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons

Yan

Guo

et al. 2015

Journal of Applied Physiology

View full text Add to dashboard Cite

In mammals, the neural control of airway smooth muscle is dominated by a subset of airway vagal preganglionic neurons in the ventrolateral medulla. These neurons are physiologically modulated by adrenergic/noradrenergic projections, and weakened α₂-adrenergic inhibition of them is indicated to participate in the pathogenesis and exacerbation of asthma. This study tests whether these neurons are modulated by α₁-adrenoceptors, and if so, how. In anesthetized adult rats, microinjection of the α₁A-adrenoceptor agonist A61603 (1 pmol) unilaterally into the medullary region containing these neurons caused a significant increase in airway resistance, which was prevented by intraperitoneal atropine (0.5 mg/kg). In rhythmically firing medullary slices of newborn rats, A61603 (10 nM) caused depolarization in both the inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons that were retrogradely labeled, and a significant increase in the spontaneous firing rate. Under voltage clamp, A61603 significantly enhanced the spontaneous excitatory inputs to both types of neurons and caused a tonic inward current in the inspiratory-activated neurons along with significantly increased peak amplitude of the inspiratory inward currents. The responses in vitro were prevented by α₁A-adrenoceptor antagonist RS100329 (1 μM), which alone significantly inhibited the spontaneous excitatory inputs to both types of the neurons. After pretreatment with tetrodotoxin (1 μM), A61603 (10 or 100 nM) had no effect on either type of neuron. We conclude that in rats, activation of α₁-adrenoceptors in the medullary region containing airway vagal preganglionic neurons increases airway vagal tone, and that this effect is primarily mediated by facilitation of the excitatory inputs to the preganglionic neurons.

show abstract

CNS determinants of sleep-related worsening of airway functions: Implications for nocturnal asthma

Cited by 11 publications

References 238 publications

Central Chemoreceptors: Locations and Functions

Central Chemoreceptors: Locations and Functions

Role of central neurotransmission and chemoreception on airway control

Activation of α₁-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons

Contact Info

Product

Resources

About

CNS determinants of sleep-related worsening of airway functions: Implications for nocturnal asthma

Cited by 11 publications

References 238 publications

Central Chemoreceptors: Locations and Functions

Central Chemoreceptors: Locations and Functions

Role of central neurotransmission and chemoreception on airway control

Activation of α1-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons

Contact Info

Product

Resources

About

Activation of α₁-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons