Neurobiology of the carotid body

López‐Barneo, José

doi:10.1016/b978-0-323-91534-2.00010-2

Cited by 11 publications

(8 citation statements)

References 253 publications

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“…Breathing frequency, tidal volume and minute volume during acute exposure to ambient 10% O 2 measured in a group of rats that had previously been treated with either chronic intermittent normoxia or CIH (see Methods) were also unchanged (Table 1). These data suggest that the CIH protocol used induced long‐term changes that preferentially affected the autonomic component (sympathetic activation and catecholamine release) of the peripheral chemoreflex (López‐Barneo, 2022; Zera et al., 2019). Although the most common experimental finding described in the literature is that CIH potentiates the hypoxic ventilatory response (HVR) (e.g.…”

Section: Resultsmentioning

confidence: 93%

Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia

Caballero-Eraso

Colinas

Sobrino

et al. 2023

The Journal of Physiology

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The carotid body (CB) is a prototypical acute oxygen (O2)‐sensing organ that mediates reflex hyperventilation and increased cardiac output in response to hypoxaemia. CB overactivation, secondary to the repeated stimulation produced by the recurrent episodes of intermittent hypoxia, is believed to contribute to the pathogenesis of sympathetic hyperactivity present in sleep apnoea patients. Although CB functional plasticity induced by chronic intermittent hypoxia (CIH) has been demonstrated, the underlying mechanisms are not fully elucidated. Here, we show that CIH induces a small increase in CB volume and rearrangement of cell types in the CB, characterized by a mobilization of immature quiescent neuroblasts, which enter a process of differentiation into mature, O2‐sensing and neuron‐like, chemoreceptor glomus cells. Prospective isolation of individual cell classes has allowed us to show that maturation of CB neuroblasts is paralleled by an upregulation in the expression of specific glomus cell genes involved in acute O2‐sensing. CIH enhances mitochondrial responsiveness to hypoxia in maturing neuroblasts as well as in glomus cells. These data provide novel perspectives on the pathogenesis of CB‐mediated sympathetic overflow that may lead to the development of new pharmacological strategies of potential applicability in sleep apnoea patients. Key points Obstructive sleep apnoea is a frequent condition in the human population that predisposes to severe cardiovascular and metabolic alterations. Activation of the carotid body, the main arterial oxygen‐sensing chemoreceptor, by repeated episodes of hypoxaemia induces exacerbation of the carotid body‐mediated chemoreflex and contributes to sympathetic overflow characteristic of sleep apnoea patients. In rats, chronic intermittent hypoxaemia induces fast neurogenesis in the carotid body with rapid activation of neuroblasts, which enter a process of proliferation and maturation into O2‐sensing chemoreceptor glomus cells. Maturing carotid body neuroblasts and glomus cells exposed to chronic intermittent hypoxia upregulate genes involved in acute O2 sensing and enhance mitochondrial responsiveness to hypoxia. These findings provide novel perspectives on the pathogenesis of carotid body‐mediated sympathetic hyperactivation. Pharmacological modulation of carotid body fast neurogenesis could help to ameliorate the deleterious effects of chronic intermittent hypoxaemia in sleep apnoea patients.

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Section: Resultsmentioning

confidence: 93%

Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia

Caballero-Eraso

Colinas

Sobrino

et al. 2023

The Journal of Physiology

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“…The CB grows severalfold in size upon exposure to chronic (days/weeks) hypoxia. 30 This well-known adaptive response ensures the sustained activation of the respiratory center that is required for acclimatization to hypoxic environments. Carotid body growth upon chronic hypoxia requires the activation of CB glomus cells, 31 which release transmitters that rapidly induce proliferation and maturation of neighboring TH-positive CB neuroblasts (immature glomus cells) followed by activation of pluripotent CB stem cells.…”

Section: Resultsmentioning

confidence: 99%

“…This Ca 2+ signal triggers the exocytotic release of transmitters that activate afferent sensory fibers impinging on brain respiratory centers. 30 We monitored changes in cytosolic [Ca 2+ ] by microfluorimetry in Fura-2-loaded dispersed glomus cells. Brief exposure to an externally applied depolarizing solution with high K + induced smooth Ca 2+ signals of large amplitude, which developed in parallel with the time course of bath solution exchange.…”

Section: Resultsmentioning

confidence: 99%

“…This noninvasive assay allows to perform a quantitative evaluation of the intrinsic O 2 sensitivity of individual glomus cells. 27 , 30 Both WT and Olfr78-deficient cells responded with graded secretory responses to variable levels of hypoxia in the bath solution (hypoxia: ∼15 mmHg; 3% O 2 : ∼30 mmHg; 6% O 2 : ∼50 mmHg; control 21% O 2 : ∼150 mmHg) ( Figure 8B and C ). However, the secretory responses of Olfr78-deficient cells are smaller than those of WT cells across the range of O 2 tensions tested; with differences statistically significant only for the lowest O 2 tensions ( Figure 8D - G ).…”

Section: Resultsmentioning

confidence: 99%

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Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice

Colinas,

Mombaerts,

López-Barneo

et al. 2024

Function

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The Olfr78 gene encodes a G-protein coupled receptor that is expressed in olfactory sensory neurons, where it functions as a conventional odorant receptor, and also in several ectopic sites, where its function is not well understood. Olfr78 is one of the most highly expressed mRNA species in glomus cells of the carotid body (CB). These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in Olfr78 knockout mice. In another study, Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. These organismal phenotypes could result from pleiotropic effects of the constitutive Olfr78 knockout mutations in the various CB cell types and/or various organs where this gene is expressed. Therefore, to further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for the phenotypic specification of mature glomus cells.

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“…From an anatomical point of view, retrotrapezoid neurons locate ventrally to the facial motor nucleus and are long known to contain central respiratory chemoreceptor neurons; that is, acid-activated neurons that maintain constant levels of arterial PCO 2 ( Figures 6A,B,F ). For more details on the physiology of retrotrapezoid neurons and other central respiratory chemoreceptor neurons, we refer to the excellent work of Nattie and Li (2012) , Guyenet and Bayliss (2015 , 2022) , Guyenet et al (2019) and Lopez-Barneo (2022) . On the other hand, neurons of the parafacial nucleus are located lateral to the facial motor nucleus.…”

Section: Development Of the Ventral Medullary Respiratory Columnmentioning

confidence: 99%

Transcription factors regulating the specification of brainstem respiratory neurons

Xia

Cui

Alonso

et al. 2022

Front. Mol. Neurosci.

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Breathing (or respiration) is an unconscious and complex motor behavior which neuronal drive emerges from the brainstem. In simplistic terms, respiratory motor activity comprises two phases, inspiration (uptake of oxygen, O2) and expiration (release of carbon dioxide, CO2). Breathing is not rigid, but instead highly adaptable to external and internal physiological demands of the organism. The neurons that generate, monitor, and adjust breathing patterns locate to two major brainstem structures, the pons and medulla oblongata. Extensive research over the last three decades has begun to identify the developmental origins of most brainstem neurons that control different aspects of breathing. This research has also elucidated the transcriptional control that secures the specification of brainstem respiratory neurons. In this review, we aim to summarize our current knowledge on the transcriptional regulation that operates during the specification of respiratory neurons, and we will highlight the cell lineages that contribute to the central respiratory circuit. Lastly, we will discuss on genetic disturbances altering transcription factor regulation and their impact in hypoventilation disorders in humans.

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Neurobiology of the carotid body

Cited by 11 publications

References 253 publications

Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia

Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia

Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice

Transcription factors regulating the specification of brainstem respiratory neurons

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