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The human carotid body in the postnatal period. (A) The 24-year-old woman. (B) The 86-year-old woman. Asterisks represent lobules. H&E stain. Left bar = 200 μm; right bar = 400 μm.
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The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuri...
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Context 1
... carotid bodies of adults resembled fetal organs in histological structure but had much more connective tissue and more prominent lobules (Figure 2A,B). In all adult carotid bodies, the type I cells also had oval or rounded nuclei. ...
Context 2
... Case 22 (the 24-year-old woman), the organ was surrounded by fibrous connective tissue along the entire perimeter (Figure 2A). At the cranial and caudal poles of the organ, this tissue had well-defined borders with layers of adipose tissue. ...
Context 3
... other cases (23-34), we found a significant increase in connective tissue in the area of bifurcation of the common carotid artery. Connective tissue grew thickly between the lobules of the carotid body and seemed to grow into previously single lobules, dividing them into smaller ones ( Figure 2B). ...
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Citations
... Structurally, the CB consists of two main cell types: chemoreceptor cells and type I cells, organized into tight clusters surrounded by supportive glial cells or type II cells. Type I cells are innervated by afferent fibers, whose soma are located at the petrosal ganglion of the glossopharyngeal nerve, and by efferent fibers emanating from the superior sympathetic cervical ganglion [31,32]. The activation of chemoreceptors in type I cells leads to depolarization and an increase in intracellular Ca 2+ concentration, followed by the release of multiple neurotransmitters and the synaptic activation of afferent nerve endings [19,[33][34][35]. ...
... Sections were processed for simultaneous detection of ASICs with specific axonal (neurofilament protein -NFP -or neuron-specific enolase -NSE) markers, supportive type II glial cell and Schwann cell (S100 protein -S100P) markers, or type I glomus cells (synaptophysin -Syn) [32,35]. Non-specific binding was reduced via incubation with a solution of 25% calf bovine serum in tris buffer solution (TBS) for 30 min. ...
The carotid body is a major peripheral chemoreceptor that senses changes in arterial blood oxygen, carbon dioxide, and pH, which is important for the regulation of breathing and cardiovascular function. The mechanisms by which the carotid body senses O2 and CO2 are well known; conversely, the mechanisms by which it senses pH variations are almost unknown. Here, we used immunohistochemistry to investigate how the human carotid body contributes to the detection of acidosis, analyzing whether it expresses acid-sensing ion channels (ASICs) and determining whether these channels are in the chemosensory glomic cells or in the afferent nerves. In ASIC1, ASIC2, and ASIC3, and to a much lesser extent ASIC4, immunoreactivity was detected in subpopulations of type I glomus cells, as well as in the nerves of the carotid body. In addition, immunoreactivity was found for all ASIC subunits in the neurons of the petrosal and superior cervical sympathetic ganglia, where afferent and efferent neurons are located, respectively, innervating the carotid body. This study reports for the first time the occurrence of ASIC proteins in the human carotid body, demonstrating that they are present in glomus chemosensory cells (ASIC1 < ASIC2 > ASIC3 > ASIC4) and nerves, presumably in both the afferent and efferent neurons supplying the organ. These results suggest that the detection of acidosis by the carotid body can be mediated via the ASIC ion channels present in the type I glomus cells or directly via sensory nerve fibers.
... The antibody letters in this table are also used in Table 3 All antibodies are supplied by Jackson ImmunoResearch (West Grove, PA, USA) , and S100B (Sigma-Aldrich, Saint Louis, MO, USA; AB_477499). Antibodies for Syp and S100B have been used as markers for type I and type II cells, respectively, in the carotid body of humans (Otlyga et al. 2021) and rats (Yokoyama et al. 2020). NTPDase2 is a plasma membrane-bound ectoenzyme that hydrolyzes extracellular nucleotides (Braun et al. 2004) and has been localized in sustentacular cells (type II cells) in the rat carotid body (Salman et al. 2017). ...
... Syp-immunoreactive type I cells were surrounded by cytoplasmic processes of S100B-immunoreactive cells in the carotid body of the Japanese monkey, suggesting that S100B-immunoreactive cells are type II cells, as is the case in humans (Otlyga et al. 2021) and rats (Yokoyama et al. 2020). Furthermore, the immunolocalization of NTP-Dase2 in S100B-immunoreactive cells suggests that type II cells express NTPDase2 in the Japanese monkey, as they do in the rat (Salman et al. 2017). ...
In the carotid body of laboratory rodents, adenosine 5'-triphosphate (ATP)-mediated transmission is regarded as critical for transmission from chemoreceptor type I cells to P2X3 purinoceptor-expressing sensory nerve endings. The present study investigated the distribution of P2X3-immunoreactive sensory nerve endings in the carotid body of the adult male Japanese monkey (Macaca fuscata) using multilabeling immunofluorescence. Immunoreactivity for P2X3 was detected in nerve endings associated with chemoreceptor type I cells immunoreactive for synaptophysin. Spherical or flattened terminal parts of P2X3-immunoreactive nerve endings were in close apposition to the perinuclear cytoplasm of synaptophysin-immunoreactive type I cells. Immunoreactivity for ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), which hydrolyzes extracellular ATP, was localized in the cell body and cytoplasmic processes of S100B-immunoreactive cells. NTPDase2-immunoreactive cells surrounded P2X3-immunoreactive terminal parts and synaptophysin-immunoreactive type I cells, but did not intrude into attachment surfaces between terminal parts and type I cells. These results suggest ATP-mediated transmission between type I cells and sensory nerve endings in the carotid body of the Japanese monkey, as well as those of rodents.
... This was accomplished using an antibody generated against either synaptophysin, a protein found in presynaptic vesicles [37], or neurofilament-L, an intermediate filament found in axons [38,39], and counterstaining the sections with TB/ammonium sulphate. As shown previously [40] type I CB cells are positive for synaptophysin, which is consistent with their role as chemosensory cells that have vesicles containing neurotransmitter that when released, stimulate sensory terminals [21,41,42]. PrP C -expressing mast cells were often located near (within 5-20 µm) synaptic terminals, axons and blood vessels in the CBs (Figure 4 (a,b)). ...
Prion diseases are fatal neurologic disorders that can be transmitted by blood transfusion. The route for neuroinvasion following exposure to infected blood is not known. Carotid bodies (CBs) are specialized chemosensitive structures that detect the concentration of blood gasses and provide feedback for the neural control of respiration. Sensory cells of the CB are highly perfused and densely innervated by nerves that are synaptically connected to the brainstem and thoracic spinal cord, known to be areas of early prion deposition following oral infection. Given their direct exposure to blood and neural connections to central nervous system (CNS) areas involved in prion neuroinvasion, we sought to determine if there were cells in the human CB that express the cellular prion protein (PrPC), a characteristic that would support CBs serving as a route for prion neuroinvasion. We collected CBs from cadaver donor bodies and determined that mast cells located in the carotid bodies express PrPC and that these cells are in close proximity to blood vessels, nerves, and nerve terminals that are synaptically connected to the brainstem and spinal cord.
Carotid body (CB) glomus cells in most mammals, including humans, contain a broad diversity of classical neurotransmitters, neuropeptides and gaseous signaling molecules as well as their cognate receptors. Among them, acetylcholine, adenosine triphosphate and dopamine have been proposed to be the main excitatory transmitters in the mammalian CB, although subsequently dopamine has been considered an inhibitory neuromodulator in almost all mammalian species except the rabbit. In addition, co-existence of biogenic amines and neuropeptides has been reported in the glomus cells, thus suggesting that they store and release more than one transmitter in response to natural stimuli. Furthermore, certain metabolic and transmitter-degrading enzymes are involved in the chemotransduction and chemotransmission in various mammals. However, the presence of the corresponding biosynthetic enzyme for some transmitter candidates has not been confirmed, and neuroactive substances like serotonin, gamma-aminobutyric acid and adenosine, neuropeptides including opioids, substance P and endothelin, and gaseous molecules such as nitric oxide have been shown to modulate the chemosensory process through direct actions on glomus cells and/or by producing tonic effects on CB blood vessels. It is likely that the fine balance between excitatory and inhibitory transmitters and their complex interactions might play a more important than suggested role in CB plasticity.
Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain Complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances Complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors.
The high prevalence of chronic noncommunicable diseases is one of the leading public health problems both in Russia and worldwide, as this group of diseases increases the risk of the development of comorbidities, development of complications, contributes significantly to the structure of primary disability, and also reduces life expectancy, requires high costs for prevention, early diagnosis and treatment of both the disease and its complications, providing patients with medicines and the necessities for the prevention of chronic noncommunicable diseases. Diabetes mellitus is one of the most common chronic nonncommunicable diseases, which according to the International Diabetes Federation by 2030 will be diagnosed in more than 700 million people. In the Russian Federation, there is also an annual increase in the incidence of diabetes in the population, but according to the data of the Federal State Budgetary Institution "Research Institute of Endocrinology" of the Ministry of Health of Russia, less than half of patients with diabetes are aware of the presence of this disease, which is one of the problems of early diagnosis of diabetes.
The objective of the study was to analyze the availability of medical care for patients with diabetes in the Russian Federation.
The carotid body (CB) is the major chemoreceptor for blood oxygen in the control of ventilation in mammals, contributing to physiological adaptation to high altitude, pregnancy, and exercise, and its hyperactivity is linked to chronic conditions such as sleep-disorder breathing, hypertension, chronic heart failure, airway constriction, and metabolic syndrome. Upon acute hypoxia (PO2=100 mmHg to <80 mmHg), K+ channels on CB glomus cells are inhibited, causing membrane depolarization to trigger Ca+2 influx and neurotransmitter release that stimulates afferent nerves. A longstanding model proposes that the CB senses hypoxia through atypical mitochondrial electron transport chain (ETC) metabolism that is more sensitive to decreases in oxygen than other tissues. This model is supported by observations that ETC inhibition by pharmacology and gene knockout activates CB sensory activity and that smaller decreases in oxygen concentration inhibit ETC activity in CB cells compared to other cells. Determining the composition of atypical ETC subunits in the CB and their specific activities is essential to delineate molecular mechanisms underlying the mitochondrial hypothesis of oxygen sensing. Here, we identify HIGD1C, a novel hypoxia inducible gene domain factor isoform, as an ETC Complex IV (CIV) protein highly and selectively expressed in glomus cells that mediates acute oxygen sensing by the CB. We demonstrate that HIGD1C negatively regulates oxygen consumption by CIV and acts with the hypoxia-induced CIV subunit COX4I2 to enhance the sensitivity of CIV to hypoxia, constituting an important component of mitochondrial oxygen sensing in the CB. Determining how HIGD1C and other atypical CIV proteins expressed in the CB work together to confer exquisite oxygen sensing to the ETC will help us better understand how tissue- and condition-specific CIV subunits contribute to physiological function and disease and allow us to potentially target these proteins to treat chronic diseases characterized by CB dysfunction.
