Carotid Body Type-I Cells Under Chronic Sustained Hypoxia: Focus on Metabolism and Membrane Excitability

Pulgar-Sepúlveda, Raúl; Varas, Rodrigo; Iturriaga, Rodrigo; Rio, Rodrigo Del; Ortiz, Fernando C.

doi:10.3389/fphys.2018.01282

Cited by 5 publications

(4 citation statements)

References 95 publications

(135 reference statements)

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“…The CB type I glomus cells secrete neurotrophic factors during development as well as in response to environmental stimuli ( 26 , 27 ), therefore we assessed brain derived neurotropic factor (BDNF) and nerve growth factor (NGF) expression in the CB and SCG neurons. Expression of BDNF was present in the CB and SCG neurons at all examined timepoints ( Figure 4A ).…”

Section: Resultsmentioning

confidence: 99%

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Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body

Roon²,

Gils³

et al. 2022

Front. Cardiovasc. Med.

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A role for cardiac sympathetic hyperinnervation in arrhythmogenesis after myocardial infarction (MI) has increasingly been recognized. In humans and mice, the heart receives cervical as well as thoracic sympathetic contributions. In mice, superior cervical ganglia (SCG) have been shown to contribute significantly to myocardial sympathetic innervation of the left ventricular anterior wall. Of interest, the SCG is situated adjacent to the carotid body (CB), a small organ involved in oxygen and metabolic sensing. We investigated the remodeling of murine SCG and CB over time after MI. Murine SCG were isolated from control mice, as well as 24 h, 3 days, 7 days and 6 weeks after MI. SCG and CBs were stained for the autonomic nervous system markers β3-tubulin, tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), as well as for the neurotrophic factors brain derived neurotropic factor (BDNF), nerve growth factor (NGF) and their tyrosine receptor kinase (pan TRK). Results show that after MI a significant increase in neuron size occurs, especially in the region bordering the CB. Co-expression of TH and ChAT is observed in SCG neuronal cells, but not in the CB. After MI, a significant decrease in ChAT intensity occurs, which negatively correlated with the increased cell size. In addition, an increase of BDNF and NGF at protein and mRNA levels was observed in both the CB and SCG. This upregulation of neurotropic factors coincides with the upregulation of their receptor within the SCG. These findings were concomitant with an increase in GAP43 expression in the SCG, which is known to contribute to axonal outgrowth and elongation. In conclusion, neuronal remodeling toward an increased adrenergic phenotype occurs in the SCG, which is possibly mediated by the CB and might contribute to pathological hyperinnervation after MI.

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Section: Resultsmentioning

confidence: 99%

“…The CB is a neural crest derived structure located at the carotid bifurcation and is the main peripheral chemoreceptor in mammals ( 26 ). It can sense and respond to changes in blood flow, O 2 - and CO 2 levels, PH as well as changes in metabolites such as glucose and lactate ( 18 , 50 ).…”

Section: Discussionmentioning

confidence: 99%

Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body

Roon²,

Gils³

et al. 2022

Front. Cardiovasc. Med.

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“…The CB is known to undergo plastic changes in response to development/aging and various environmental stimuli, including chronic intermittent/sustained hypoxia. Its function is strictly related to these dynamic modifications (Iturriaga et al, 2006;López-Barneo et al, 2009;Dmitrieff et al, 2011;Kumar and Prabhakar, 2012;Bavis et al, 2013;Del Rio et al, 2014;Pulgar-Sepúlveda et al, 2018;Bavis et al, 2019;Liu et al, 2019), which can be also ascribed to the specific receptor behavior.…”

Section: Discussionmentioning

confidence: 99%

Experimental Evidence of A2A–D2 Receptor–Receptor Interactions in the Rat and Human Carotid Body

et al. 2021

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Adenosine A2A receptors (A2AR) and dopamine D2 receptors (D2R) are known to be involved in the physiological response to hypoxia, and their expression/activity may be modulated by chronic sustained or intermittent hypoxia. To date, A2AR and D2R can form transient physical receptor–receptor interactions (RRIs) giving rise to a dynamic equilibrium able to influence ligand binding and signaling, as demonstrated in different native tissues and transfected mammalian cell systems. Given the presence of A2AR and D2R in type I cells, type II cells, and afferent nerve terminals of the carotid body (CB), the aim of this work was to demonstrate here, for the first time, the existence of A2AR–D2R heterodimers by in situ proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase/S100 colocalization indicated the formation of A2AR–D2R heterodimers in type I and II cells of the CB; the presence of A2AR–D2R heterodimers also in afferent terminals is also suggested by PLA signal distribution. RRIs could play a role in CB dynamic modifications and plasticity in response to development/aging and environmental stimuli, including chronic intermittent/sustained hypoxia. Exploring other RRIs will allow for a broad comprehension of the regulative mechanisms these interactions preside over, with also possible clinical implications.

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“…Studies in fetal sheep have extended our understanding of the hypoxaemic response, demonstrating that peripheral vasoconstriction causes fetal cardiac output redistribution in favour of vital organs, such as the fetal brain, which is then augmented by the vasoconstrictor hormones such as catecholamines (Giussani, 2016 ). Cardiac output redistribution is initiated when blood‐borne signals of hypoxaemia and hypercapnia activate the carotid body type 1 cells (glomus cells; chief cells or type I cells) (Pulgar‐Sepúlveda et al., 2018 ). The carotid bodies are innervated by the carotid sinus nerve branch of the glossopharyngeal nerve and project centrally into the NTS through the ST (Paxinos et al., 2012 ), with carotid sinus nerve firing proportional to the severity of hypoxia (Lopez‐Barneo et al., 2008 ).…”

Section: Brainstem Response To Hypoxiamentioning

confidence: 99%

Does fetal growth restriction induce neuropathology within the developing brainstem?

Ahmadzadeh,

Polglase,

Stojanovska

et al. 2023

The Journal of Physiology

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Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered neurological, cardiovascular and respiratory development, some of which may be pathophysiological, particularly for neonatal life. The brainstem is the critical site of cardiovascular, respiratory and autonomic control, but there is little information describing how chronic hypoxaemia and the resulting FGR may affect brainstem neurodevelopment. This review provides an overview of the brainstem‐specific consequences of acute and chronic hypoxia, and what is known in FGR. In addition, we discuss how brainstem structural alterations may impair functional control of the cardiovascular and respiratory systems. Finally, we highlight the clinical and translational findings of the potential roles of the brainstem in maintaining cardiorespiratory adaptation in the transition from fetal to neonatal life under normal conditions and in response to the pathological environment that arises during development in growth‐restricted infants. This review emphasises the crucial role that the brainstem plays in mediating cardiovascular and respiratory responses during fetal and neonatal life. We assess whether chronic fetal hypoxaemia might alter structure and function of the brainstem, but this also serves to highlight knowledge gaps regarding FGR and brainstem development. image

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Carotid Body Type-I Cells Under Chronic Sustained Hypoxia: Focus on Metabolism and Membrane Excitability

Cited by 5 publications

References 95 publications

Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body

Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body

Experimental Evidence of A2A–D2 Receptor–Receptor Interactions in the Rat and Human Carotid Body

Does fetal growth restriction induce neuropathology within the developing brainstem?

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