To see the other types of publications on this topic, follow the link: Afferent pathways – Diseases.
Journal articles on the topic 'Afferent pathways – Diseases'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Afferent pathways – Diseases.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Mazzone, Stuart B., and Bradley J. Undem. "Vagal Afferent Innervation of the Airways in Health and Disease." Physiological Reviews 96, no. 3 (July 2016): 975–1024. http://dx.doi.org/10.1152/physrev.00039.2015.
Full textAbstract:
Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions.
2
Canning, Brendan J. "Reflex regulation of airway smooth muscle tone." Journal of Applied Physiology 101, no. 3 (September 2006): 971–85. http://dx.doi.org/10.1152/japplphysiol.00313.2006.
Full textAbstract:
Autonomic nerves in most mammalian species mediate both contractions and relaxations of airway smooth muscle. Cholinergic-parasympathetic nerves mediate contractions, whereas adrenergic-sympathetic and/or noncholinergic parasympathetic nerves mediate relaxations. Sympathetic-adrenergic innervation of human airway smooth muscle is sparse or nonexistent based on histological analyses and plays little or no role in regulating airway caliber. Rather, in humans and in many other species, postganglionic noncholinergic parasympathetic nerves provide the only relaxant innervation of airway smooth muscle. These noncholinergic nerves are anatomically and physiologically distinct from the postganglionic cholinergic parasympathetic nerves and differentially regulated by reflexes. Although bronchopulmonary vagal afferent nerves provide the primary afferent input regulating airway autonomic nerve activity, extrapulmonary afferent nerves, both vagal and nonvagal, can also reflexively regulate autonomic tone in airway smooth muscle. Reflexes result in either an enhanced activity in one or more of the autonomic efferent pathways, or a withdrawal of baseline cholinergic tone. These parallel excitatory and inhibitory afferent and efferent pathways add complexity to autonomic control of airway caliber. Dysfunction or dysregulation of these afferent and efferent nerves likely contributes to the pathogenesis of obstructive airways diseases and may account for the pulmonary symptoms associated with extrapulmonary disorders, including gastroesophageal reflux disease, cardiovascular disease, and rhinosinusitis.
3
Korneva, E. A. "Pathways of neuro-immune communication: past and present time, clinical application." Medical Immunology (Russia) 22, no. 3 (May 21, 2020): 405–18. http://dx.doi.org/10.15789/1563-0625-pon-1974.
Full textAbstract:
Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain.
4
Burke, Melissa L., Michael de Veer, Jill Pleasance, Melanie Neeland, Martin Elhay, Paul Harrison, and Els Meeusen. "Innate immune pathways in afferent lymph following vaccination with poly(I:C)-containing liposomes." Innate Immunity 20, no. 5 (September 17, 2013): 501–10. http://dx.doi.org/10.1177/1753425913501213.
Full text
5
Vibert, D., R. Häusler, and A. B. Safran. "Subjective visual vertical in peripheral unilateral vestibular diseases*." Journal of Vestibular Research 9, no. 2 (April 1, 1999): 145–52. http://dx.doi.org/10.3233/ves-1999-9209.
Full textAbstract:
In humans, the perception of vertical is provided by input from various sensorineural organs and pathways: vision, eye-movements, and proprioceptive and vestibular cues, particularly from the otolithic organs and graviceptive pathways. Well known in several types of brainstem lesions, subjective visual vertical (SVV) abnormalities may also be observed after peripheral vestibular lesions, such as surgical deafferentation, with a deviation directed toward the operated ear. Subjective visual vertical abnormalities are presumably related to a lesion of the otolithic organs and/or to changes in the afferent graviceptive pathways. The goal of this prospective study was to measure the SVV and to define the influence of the otolithic organs in patients suffering from various types of peripheral vestibular diseases: unilateral sudden cochleo-vestibular loss, so-called “viral labyrinthitis” (VL), sudden idiopathic unilateral peripheral vestibular loss, so-called “vestibular neuritis” (Ne). Data were compared with findings after unilateral surgical deafferentations such as vestibular neurectomy (VN) and labyrinthectomy (Lab). Subjective visual vertical was measured with a binocular test (vertical frame) and a monocular test (Maddox rod). In all patients, after VN and Lab, the SVV showed a 10 – 30 ∘ tilt with the vertical frame (N: 0 ± 2 ∘ ), 5 – 15 ∘ with the Maddox rod (N: 0 ± 4 ∘ ). With the vertical frame, SVV was tilted > 2 ∘ in VL (47%) VL (41%) Our results demonstrate that SVV is frequently tilted in acute peripheral vestibulopathies such as VL and Ne. These findings suggest that otolithic function is implicated in the deficit depending on the extent and/or the localisation of the peripheral vestibular lesion.
6
Noh, Mi, Hee-Seong Jang, Jinu Kim, and Babu Padanilam. "Renal Sympathetic Nerve-Derived Signaling in Acute and Chronic Kidney Diseases." International Journal of Molecular Sciences 21, no. 5 (February 28, 2020): 1647. http://dx.doi.org/10.3390/ijms21051647.
Full textAbstract:
The kidney is innervated by afferent sensory and efferent sympathetic nerve fibers. Norepinephrine (NE) is the primary neurotransmitter for post-ganglionic sympathetic adrenergic nerves, and its signaling, regulated through adrenergic receptors (AR), modulates renal function and pathophysiology under disease conditions. Renal sympathetic overactivity and increased NE level are commonly seen in chronic kidney disease (CKD) and are critical factors in the progression of renal disease. Blockade of sympathetic nerve-derived signaling by renal denervation or AR blockade in clinical and experimental studies demonstrates that renal nerves and its downstream signaling contribute to progression of acute kidney injury (AKI) to CKD and fibrogenesis. This review summarizes our current knowledge of the role of renal sympathetic nerve and adrenergic receptors in AKI, AKI to CKD transition and CKDand provides new insights into the therapeutic potential of intervening in its signaling pathways.
7
Baj, Andreina, Michela Bistoletti, Annalisa Bosi, Elisabetta Moro, Cristina Giaroni, and Francesca Crema. "Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders." Toxins 11, no. 8 (July 31, 2019): 449. http://dx.doi.org/10.3390/toxins11080449.
Full textAbstract:
Visceral pain, of which the pathogenic basis is currently largely unknown, is a hallmark symptom of both functional disorders, such as irritable bowel syndrome, and inflammatory bowel disease. Intrinsic sensory neurons in the enteric nervous system and afferent sensory neurons of the dorsal root ganglia, connecting with the central nervous system, represent the primary neuronal pathways transducing gut visceral pain. Current pharmacological therapies have several limitations, owing to their partial efficacy and the generation of severe adverse effects. Numerous cellular targets of visceral nociception have been recognized, including, among others, channels (i.e., voltage-gated sodium channels, VGSCs, voltage-gated calcium channels, VGCCs, Transient Receptor Potential, TRP, and Acid-sensing ion channels, ASICs) and neurotransmitter pathways (i.e., GABAergic pathways), which represent attractive targets for the discovery of novel drugs. Natural biologically active compounds, such as marine toxins, able to bind with high affinity and selectivity to different visceral pain molecular mediators, may represent a useful tool (1) to improve our knowledge of the physiological and pathological relevance of each nociceptive target, and (2) to discover therapeutically valuable molecules. In this review we report the most recent literature describing the effects of marine toxin on gastrointestinal visceral pain pathways and the possible clinical implications in the treatment of chronic pain associated with gut diseases.
8
Guilloteau, P., V. Le Meuth-Metzinger, J. Morisset, and R. Zabielski. "Gastrin, cholecystokinin and gastrointestinal tract functions in mammals." Nutrition Research Reviews 19, no. 2 (December 2006): 254–83. http://dx.doi.org/10.1017/s0954422407334082.
Full textAbstract:
The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK1and CCK2receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.
9
Vits, Sabine, Elvir Cesko, Paul Enck, Uwe Hillen, Dirk Schadendorf, and Manfred Schedlowski. "Behavioural conditioning as the mediator of placebo responses in the immune system." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1572 (June 27, 2011): 1799–807. http://dx.doi.org/10.1098/rstb.2010.0392.
Full textAbstract:
Current placebo research postulates that conditioning processes are one of the major mechanisms of the placebo response. Behaviourally conditioned changes in peripheral immune functions have been demonstrated in experimental animals, healthy subjects and patients. The physiological mechanisms responsible for this ‘learned immune response’ are not yet fully understood, but some relevant afferent and efferent pathways in the communication between the brain and the peripheral immune system have been identified. In addition, possible benefits and applicability in clinical settings have been demonstrated where behaviourally conditioned immunosuppression attenuated the exacerbation of autoimmune diseases, prolonged allograft survival and affected allergic responses. Here, we summarize data describing the mechanisms and the potential clinical benefit of behaviourally conditioned immune functions, with particular focus on learned placebo effects on allergic reactions.
10
Gaier, E. D., R. M. Rodriguiz, J. Zhou, M. Ralle, W. C. Wetsel, B. A. Eipper, and R. E. Mains. "In vivo and in vitro analyses of amygdalar function reveal a role for copper." Journal of Neurophysiology 111, no. 10 (May 15, 2014): 1927–39. http://dx.doi.org/10.1152/jn.00631.2013.
Full textAbstract:
Mice with a single copy of the peptide amidating monooxygenase ( Pam) gene (PAM+/−) are impaired in contextual and cued fear conditioning. These abnormalities coincide with deficient long-term potentiation (LTP) at excitatory thalamic afferent synapses onto pyramidal neurons in the lateral amygdala. Slice recordings from PAM+/− mice identified an increase in GABAergic tone (Gaier ED, Rodriguiz RM, Ma XM, Sivaramakrishnan S, Bousquet-Moore D, Wetsel WC, Eipper BA, Mains RE. J Neurosci 30: 13656–13669, 2010). Biochemical data indicate a tissue-specific deficit in Cu content in the amygdala; amygdalar expression of Atox-1 and Atp7a, essential for transport of Cu into the secretory pathway, is reduced in PAM+/− mice. When PAM+/− mice were fed a diet supplemented with Cu, the impairments in fear conditioning were reversed, and LTP was normalized in amygdala slice recordings. A role for endogenous Cu in amygdalar LTP was established by the inhibitory effect of a brief incubation of wild-type slices with bathocuproine disulfonate, a highly selective, cell-impermeant Cu chelator. Interestingly, bath-applied CuSO4 had no effect on excitatory currents but reversibly potentiated the disynaptic inhibitory current. Bath-applied CuSO4 was sufficient to potentiate wild-type amygdala afferent synapses. The ability of dietary Cu to affect signaling in pathways that govern fear-based behaviors supports an essential physiological role for Cu in amygdalar function at both the synaptic and behavioral levels. This work is relevant to neurological and psychiatric disorders in which disturbed Cu homeostasis could contribute to altered synaptic transmission, including Wilson's, Menkes, Alzheimer's, and prion-related diseases.
11
Liersch, Ruediger, and Michael Detmar. "Lymphangiogenesis in development and disease." Thrombosis and Haemostasis 98, no. 08 (2007): 304–10. http://dx.doi.org/10.1160/th07-04-0238.
Full textAbstract:
SummaryThe lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.
12
Damiani, Daniel, Ana Maria Nascimento, and Vanessa Gonçalves Pires. "Unveiling the Insular Lobe of Reil: Neurophysiological and Anatomical Features." Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 38, no. 02 (April 5, 2019): 117–23. http://dx.doi.org/10.1055/s-0039-1685153.
Full textAbstract:
AbstractThe insular lobe has long been investigated, from its anatomical descriptions to its neurophysiological activity. Located in a central location, the insular lobe participates in several afferent and efferent pathways, forming part of the eloquent and fundamental structures that make up the central core of the brain. The lobe of the insula has participation in language function, such as speech, sensory (e.g., taste), limbic, autonomic (visceral), also forming part of complex associative circuits, including part of the circuits of mirror neurons. Several functional descriptions attributed to the insular lobe have been made in patients suffering from cerebrovascular diseases, as well as in those with epilepsy. Much progress and many descriptions have also been made in patients with tumors. Despite much information already available about the insular lobe, it is likely that much will be discovered in the coming years.
13
Chollet, Catherine, Sandrine Placier, Christos Chatziantoniou, Annette Hus-Citharel, Nathalie Caron, Ronan Roussel, François Alhenc-Gelas, and Nadine Bouby. "Genetically increased angiotensin I-converting enzyme alters peripheral and renal vascular reactivity to angiotensin II and bradykinin in mice." American Journal of Physiology-Heart and Circulatory Physiology 314, no. 2 (February 1, 2018): H350—H358. http://dx.doi.org/10.1152/ajpheart.00356.2017.
Full textAbstract:
Angiotensin I-converting enzyme (ACE) levels in humans are under strong genetic influence. Genetic variation in ACE has been linked to risk for and progression of cardiovascular and renal diseases. Causality has been documented in genetically modified mice, but the mechanisms underlying causality are not completely elucidated. To further document the vascular and renal consequences of a moderate genetic increase in ACE synthesis, we studied genetically modified mice carrying three copies of the ACE gene (three-copy mice) and littermate wild-type animals (two-copy mice). We investigated peripheral and renal vascular reactivity to angiotensin II and bradykinin in vivo by measuring blood pressure and renal blood flow after intravenous administration and also reactivity of isolated glomerular arterioles by following intracellular Ca2+ mobilization. Carrying three copies of the ACE gene potentiated the systemic and renal vascular responses to angiotensin II over the whole range of peptide concentration tested. Consistently, the response of isolated glomerular afferent arterioles to angiotensin II was enhanced in three-copy mice. In these mice, signaling pathways triggered by endothelial activation by bradykinin or carbachol in glomerular arterioles were also altered. Although the nitric oxide (NO) synthase (NOS)/NO pathway was not functional in arterioles of two-copy mice, in muscular efferent arterioles of three-copy mice NOS3 gene expression was induced and NO mediated the effect of bradykinin or carbachol. These data document new and unexpected vascular consequences of a genetic increase in ACE synthesis. Enhanced vasoconstrictor effect of angiotensin II may contribute to the risk for cardiovascular and renal diseases linked to genetically high ACE levels. NEW & NOTEWORTHY A moderate genetic increase in angiotensin I-converting enzyme (ACE) in mice similar to the effect of the ACE gene D allele in humans unexpectedly potentiates the systemic and renal vasoconstrictor responses to angiotensin II. It also alters the endothelial signaling pathways triggered by bradykinin or carbachol in glomerular efferent arterioles.
14
Szabóová, R. "Optimal Criteria for the Selection of Probiotics, Based on their Mode of Action." Folia Veterinaria 63, no. 4 (December 1, 2019): 60–69. http://dx.doi.org/10.2478/fv-2019-0039.
Full textAbstract:
Abstract The objective of this review was to discuss some of the criteria which influence the selection of microorganisms with probiotic properties based on their mode of action. The most common bacteria that belong to the “group” probiotics are the Lactobacillus and Bifidobacterium species/strains. Probiotics have benefits and effects by their mechanism of action in different axial locations such as: producing substances, influencing immune function and response, modification as well as maintenance of a healthy population of microorganisms in the intestinal environment. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases Potential peripheral pathways that link probiotic ingestion in the brain function are focused on the role of the vagal afferent nerve signalling and changes in the cerebral levels of neuromodulators. The application of probiotic microorganisms represents a way to effectively influence the composition of the intestinal microbiome and the immune system of the host, as well as they can be considered as a suitable alternative to influence a healthy quality of life.
15
Halmos, Tamás, and Ilona Suba. "The role of the brain in the regulation of metabolism and energy expenditure: the central role of insulin, the insulin resistance of the brain." Orvosi Hetilap 152, no. 3 (January 2011): 83–91. http://dx.doi.org/10.1556/oh.2011.28981.
Full textAbstract:
Regulatory role of the brain in energy expenditure, appetite, glucose metabolism, and central effects of insulin has been prominently studied. Certain neurons in the hypothalamus increase or decrease appetite via orexigenes and anorexigenes, regulating energy balance and food intake. Hypothalamus is the site of afferent and efferent stimuli between special nuclei and beta- and alpha cells, and it regulates induction/inhibition of glucose output from the liver. Incretines, produced in intestine and in certain brain cells (brain-gut hormones), link to special receptors in the hypothalamus. Central role of insulin has been proved both in animals and in humans. Insulin gets across the blood-brain barrier, links to special hypothalamic receptors, regulating peripheral glucose metabolism. Central glucose sensing, via “glucose-excited” and “glucose-inhibited” cells have outstanding role. Former are active in hyperglycaemia, latter in hypoglycaemia, via influencing beta– and alpha cells, independently of traditional metabolic pathways. Evidence of brain insulin resistance needs centrally acting drugs, paradigm changes in therapy and prevention of metabolic syndrome, diabetes, cardiovascular and oncological diseases. Orv. Hetil., 2011, 152, 83–91.
16
Chen, Shuping, Shubin Wang, Peijing Rong, Junying Wang, Lina Qiao, Xiumei Feng, Junling Liu, and Jianliang Zhang. "Acupuncture for Visceral Pain: Neural Substrates and Potential Mechanisms." Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/609594.
Full textAbstract:
Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. Despite much advances, the pathophysiological mechanism is still poorly understood comparing with its somatic counterpart and, as a result, the therapeutic efficacy is usually unsatisfactory. Acupuncture has long been used for the management of numerous disorders in particular pain and visceral pain, characterized by the high therapeutic benefits and low adverse effects. Previous findings suggest that acupuncture depresses pain via activation of a number of neurotransmitters or modulators including opioid peptides, serotonin, norepinephrine, and adenosine centrally and peripherally. It endows us, by advancing the understanding of the role of ion channels and gut microbiota in pain process, with novel perspectives to probe the mechanisms underlying acupuncture analgesia. In this review, after describing the visceral innervation and the relevant afferent pathways, in particular the ion channels in visceral nociception, we propose three principal mechanisms responsible for acupuncture induced benefits on visceral pain. Finally, potential topics are highlighted regarding the future studies in this field.
17
Otto, Ellen, Paul-Richard Knapstein, Denise Jahn, Jessika Appelt, Karl-Heinz Frosch, Serafeim Tsitsilonis, and Johannes Keller. "Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases." International Journal of Molecular Sciences 21, no. 14 (July 13, 2020): 4946. http://dx.doi.org/10.3390/ijms21144946.
Full textAbstract:
As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs. This review summarizes clinical and experimental observations reported for the crosstalk of brain and bone, followed by a detailed overview of their molecular bases. While brain-derived molecules affecting bone include central regulators, transmitters of the sympathetic, parasympathetic and sensory nervous system, bone-derived mediators altering brain function are released from bone cells and the bone marrow. Although the main pathways of the brain-bone crosstalk remain ‘efferent’, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial ‘afferent’ regulator of cerebral development, function and pathophysiology. Therefore, unraveling the physiological and pathological bases of brain-bone interactions revealed promising pharmacologic targets and novel treatment strategies promoting concurrent brain and bone recovery.
18
Ru, F., L. Surdenikova, M. Brozmanova, and M. Kollarik. "Adenosine-induced activation of esophageal nociceptors." American Journal of Physiology-Gastrointestinal and Liver Physiology 300, no. 3 (March 2011): G485—G493. http://dx.doi.org/10.1152/ajpgi.00361.2010.
Full textAbstract:
Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A1 receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A1 and/or A2A receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A1 receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A2A receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A1 receptor while the placodes-derived esophageal nociceptors can be activated via A1 and/or A2A receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.
19
Campos-Ríos, Ana, Lola Rueda-Ruzafa, Salvador Herrera-Pérez, Paula Rivas-Ramírez, and José Antonio Lamas. "Tetrodotoxin: A New Strategy to Treat Visceral Pain?" Toxins 13, no. 7 (July 16, 2021): 496. http://dx.doi.org/10.3390/toxins13070496.
Full textAbstract:
Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.
20
Akiyama, Tasuku, Mirela Iodi Carstens, and E. Carstens. "Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model." Journal of Neurophysiology 105, no. 6 (June 2011): 2811–17. http://dx.doi.org/10.1152/jn.01124.2010.
Full textAbstract:
Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.
21
Carlström, Mattias, Christopher S. Wilcox, and William J. Arendshorst. "Renal Autoregulation in Health and Disease." Physiological Reviews 95, no. 2 (April 2015): 405–511. http://dx.doi.org/10.1152/physrev.00042.2012.
Full textAbstract:
Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]ioccurs predominantly by Ca2+influx through L-type voltage-operated Ca2+channels (VOCC). Increased [Ca2+]iactivates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.
22
Vits, Sabine, and Manfred Schedlowski. "Learned Placebo Effects in the Immune System." Zeitschrift für Psychologie 222, no. 3 (January 2014): 148–53. http://dx.doi.org/10.1027/2151-2604/a000184.
Full textAbstract:
Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.
23
Hockley, James R. F., Ewan St John Smith, and David C. Bulmer. "Human visceral nociception: findings from translational studies in human tissue." American Journal of Physiology-Gastrointestinal and Liver Physiology 315, no. 4 (October 1, 2018): G464—G472. http://dx.doi.org/10.1152/ajpgi.00398.2017.
Full textAbstract:
Peripheral sensitization of nociceptors during disease has long been recognized as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitization is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular, irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans and, in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons, the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurons combined with unbiased RNA-sequencing approaches have revealed fundamental differences in not only receptor/channel expression but also peripheral pain pathways.
24
Hadamitzky, Martin, Laura Lückemann, Gustavo Pacheco-López, and Manfred Schedlowski. "Pavlovian Conditioning of Immunological and Neuroendocrine Functions." Physiological Reviews 100, no. 1 (January 1, 2020): 357–405. http://dx.doi.org/10.1152/physrev.00033.2018.
Full textAbstract:
The phenomenon of behaviorally conditioned immunological and neuroendocrine functions has been investigated for the past 100 yr. The observation that associative learning processes can modify peripheral immune functions was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system’s function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. With the employment of a taste-avoidance paradigm in rats, this phenomenon was rediscovered 45 yr ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be modulated via associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provide fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient’s benefit.
25
Savoie, Chantal, Chi-Chung Chan, Ian W. Rodger, and Annette Robichaud. "Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats." Canadian Journal of Physiology and Pharmacology 78, no. 9 (September 1, 2000): 708–13. http://dx.doi.org/10.1139/y00-046.
Full textAbstract:
The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the treatment of inflammation and pulmonary diseases is limited by their side effects: nausea and vomiting. We studied the effect of three structurally diverse PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered at 1, 10, or 100 µg/kg (iv) 15 min prior to the induction of bradycardia by an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal electrical stimulation. At 100 µg/kg, RS14203 significantly potentiated the 2-methyl-5-HT response. No statistically significant effects were observed with (R)-rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1-100 µg/kg iv) did not affect the bradycardia induced by vagal electrical stimulation. Consequently, our results show that RS14203 selectively facilitates serotoninergic neurotransmission in vagal afferent fibers. The emetic action of RS14203 may be mediated by this mechanism.Key words: PDE4 inhibitors, von Bezold-Jarisch reflex, emesis, vagal afferent and efferent fibres, bradycardia.
26
Poliacek, I., M. Simera, V. Calkovsky, and J. Jakus. "Upper Airway Control in Airway Defense." Acta Medica Martiniana 16, no. 1 (April 1, 2016): 5–16. http://dx.doi.org/10.1515/acm-2016-0001.
Full textAbstract:
AbstractUpper airways (UA) are an organic component of the respiratory tract, they serve to respiration, respiratory tract protection and defense, phonation, deglutition, etc. The functions of UA are regulated by motor control of the oral, pharyngeal, and laryngeal muscles.UA typically stiffen and widen during inspiration mainly due to the activation of the alae nasi, genioglossus m., pharyngeal dilators, and laryngeal abductors. These and other UA muscles (e.g. laryngeal and pharyngeal constrictors) may express varoius activity patterns, actively shaping UA depending on species, arousal, respiratory drive, and behavior being executed. E.g. during coughing and sneezing laryngeal movement consists of abductions in inspiration and expiration and adductions in compression and subsequent constriction phase. The cricopharyngeus m., in cough expiration the superior pharyngeal constrictor and in the sneeze expiration the styloglossus and levator veli palatini m. are activated. Unlike in breathing or coughing, where UA serve to respiration-protection-defense, the pharyngeal phase of swallowing is essentially made by the coordinated action of a number of UA muscles.Motoneurons driving the UA muscles are located primarily in the hypoglossal and ambigual nuclei. Motor pattern of individual motoneuronal pools is determined by activation-inhibition-modulation from pre-motoneurons and other upstream neurons of the reflex circuits. Laryngeal and hypoglossal nerve activity is during breathing under command of respiratory central pattern generator. UA muscles are driven in inspiration primarily from augmenting, less from decrementing and constant inspiratory neurons. Number of additional inputs is involved in UA regulation during expirations and other motor behaviors. Anatomical and functional studies pointed out number of brainstem areas, such as the regions of solitary tract nucleus, hypoglossal ncl., trigeminal ncl., lateral tegmental field, raphé, the ventral and ventrolateral medulla, pontine parabrachial region, etc. with neurons related to UA motor control.Abundant connectivity of the neuronal network that controls UA patency employs almost all kind of receptors and neurotransmitter/neuromodulator systems. Among large number of diseases and disorders that relate to UA, primarily cholinergic, norepinephrine, and serotonergic tonic drives are implicated in those resulted from the reduced UA tone. Pharmacological and frequently simple surgical interventions may improve these conditions (snore, obturation) in patients. Recently, besides medicinal treatment, conditional procedures incorporating an exercise and practice, stimulation of appropriate afferent pathways, and combining reflex responses may offer promising therapies.
27
Tanaka, Shinji, Chikara Abe, Stephen B. G. Abbott, Shuqiu Zheng, Yusuke Yamaoka, Jonathan E. Lipsey, Nataliya I. Skrypnyk, et al. "Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury." Proceedings of the National Academy of Sciences 118, no. 12 (March 18, 2021): e2021758118. http://dx.doi.org/10.1073/pnas.2021758118.
Full textAbstract:
Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs. VNS broadly stimulates these fibers without specificity. We used optogenetics to selectively stimulate vagus efferent or afferent fibers. Anterograde efferent fiber stimulation or anterograde (centripetal) sensory afferent fiber stimulation both conferred kidney protection from ischemia–reperfusion injury. We identified the C1 neurons–sympathetic nervous system–splenic nerve–spleen–kidney axis as the downstream pathway of vagus afferent fiber stimulation. Our study provides a map of the neural circuits important for kidney protection induced by VNS, which is critical for the safe and effective clinical application of VNS for protection from acute kidney injury.
28
He, Wei, Xiaoyu Wang, Hong Shi, Hongyan Shang, Liang Li, Xianghong Jing, and Bing Zhu. "Auricular Acupuncture and Vagal Regulation." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/786839.
Full textAbstract:
Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the “auriculovagal afferent pathway” (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated.
29
Farmer, Adam D., and Qasim Aziz. "Mechanisms of visceral pain in health and functional gastrointestinal disorders." Scandinavian Journal of Pain 5, no. 2 (April 1, 2014): 51–60. http://dx.doi.org/10.1016/j.sjpain.2014.01.002.
Full textAbstract:
AbstractBackground and aimsChronic visceral pain is common both in patients with identifiable organic disease and also in those without any structural, biochemical or immunological abnormality such as in the functional gastrointestinal disorders (FGIDs). We aim to provide a contemporaneous summary of pathways involved in visceral nociception and how a variety of mechanisms may influence an individual’s experience of visceral pain.MethodsIn this narrative review, we have brought together evidence through a detailed search of Medline in addition to using our experience and exposure to recent research developments from ourselves and other research groups.ResultsFGIDs are a heterogeneous group of disorders whose aetiology largely remains an enigma. The germane hypothesis for the genesis and maintenance of chronic visceral pain in FGIDs is the concept of visceral hypersensitivity. A number of peripheral and central mechanisms have been proposed to account for this epiphenomenon. In the periphery, inflammatory mediators activate and sensitize nociceptive afferent nerves by reducing their transduction thresholds and by inducing the expression and recruitment of hitherto silent nociceptors culminating in an increase in pain sensitivity at the site of injury known as primary hyperalgesia. Centrally, secondary hyperalgesia, defined as an increase in pain sensitivity in anatomically distinct sites, occurs at the level of the spinal dorsal horn. Moreover, the stress responsive physiological systems, genetic and psychological factors may modulate the experience of visceral pain. We also address some novel aetiological concepts in FGIDs, namely the gastrointestinal microbiota, connective tissue abnormalities and the gastrointestinal neuromuscular disorders. Firstly, the gastrointestinal microbiota is a diverse and dynamic ecosystem, that safeguards the host from external pathogens, aids in the metabolism of polysaccharides and lipids, modulates intestinal motility, in addition to modulating visceral perception. Secondly, connective tissue disorders, which traditionally have been considered to be confined largely to the musculoskeletal system, have an increasing evidence base demonstrating the presence of visceral manifestations. Since the sensorimotor apparatus of the GI tract is embedded within connective tissue it should not be surprising that such disorder may result in visceral pain and abnormal gut motility. Thirdly, gastrointestinal neuromuscular diseases refer to a heterogeneous group of disorders in which symptoms arise from impaired GI motor activity often manifesting as abnormal transit with or without radiological evidence of transient or persistent dilation of the viscera. Although a number of these are readily recognizable, such as achalasia or Hirschsprung’s disease, the cause in a number of patients is not. An international working group has recently addressed this “gap”, providing a comprehensive morphologically based diagnostic criteria.Conclusions/implicationsAlthough marked advances have been made in understanding the mechanisms that contribute to the development and maintenance of visceral pain, many interventions have failed to produce tangible improvement in patient outcomes. In the last part of this review we highlight an emerging approach that has allowed the definition and delineation of temporally stable visceral pain clusters, which may improve participant homogeneity in future studies, potentially facilitate stratification of treatment in FGID and lead to improvements in diagnostic criteria and outcomes.
30
Ye, Feng, Yi Liu, Shiying Li, Sujuan Zhang, Robert D. Foreman, and Jiande DZ Chen. "Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway." American Journal of Physiology-Gastrointestinal and Liver Physiology 318, no. 3 (March 1, 2020): G574—G581. http://dx.doi.org/10.1152/ajpgi.00255.2019.
Full textAbstract:
Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450–500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway. NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.
31
De Miguel, Carmen, and Jennifer S. Pollock. "Does endoplasmic reticulum stress mediate endothelin-1-induced renal inflammation?" American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 305, no. 2 (July 15, 2013): R107—R109. http://dx.doi.org/10.1152/ajpregu.00184.2013.
Full textAbstract:
Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide known. It exerts its actions through two pharmacologically different receptors: ETA and ETB receptors. In the renal vasculature, there is a majority of ETB receptors in the efferent arteriole, whereas a greater amount of ETA receptors are located in the afferent arteriole. The nephron is rich in ETB receptors, especially in the thick ascending limb and collecting ducts, while containing a smaller amount of ETA receptors. High levels of circulating or renal ET-1 have been described in cardiovascular diseases such as hypertension or diabetes, diseases also associated to renal inflammation. Despite extensive evidence associating high levels of ET-1 to increased renal inflammation, the molecular mechanism(s) by which ET-1 leads to renal immune infiltration and/or immune activation remains unknown. In this minireview, we propose that the ET-1/ETA pathway mediates an increase in renal endoplasmic reticulum (ER) stress, initially a survival mechanism that if prolonged, leads to the eventual death of the cell via apoptosis.
32
Haxhiu, Musa A., Prabha Kc, Constance T. Moore, Sandra S. Acquah, Christopher G. Wilson, Syed I. Zaidi, V. John Massari, and Donald G. Ferguson. "Brain stem excitatory and inhibitory signaling pathways regulating bronchoconstrictive responses." Journal of Applied Physiology 98, no. 6 (June 2005): 1961–82. http://dx.doi.org/10.1152/japplphysiol.01340.2004.
Full textAbstract:
This review summarizes recent work on two basic processes of central nervous system (CNS) control of cholinergic outflow to the airways: 1) transmission of bronchoconstrictive signals from the airways to the airway-related vagal preganglionic neurons (AVPNs) and 2) regulation of AVPN responses to excitatory inputs by central GABAergic inhibitory pathways. In addition, the autocrine-paracrine modulation of AVPNs is briefly discussed. CNS influences on the tracheobronchopulmonary system are transmitted via AVPNs, whose discharge depends on the balance between excitatory and inhibitory impulses that they receive. Alterations in this equilibrium may lead to dramatic functional changes. Recent findings indicate that excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second-order neurons within the nucleus of the solitary tract (NTS), via a glutamate-AMPA signaling pathway. These neurons, using the same neurotransmitter-receptor unit, transmit information to the AVPNs, which in turn convey the central command to airway effector organs: smooth muscle, submucosal secretory glands, and the vasculature, through intramural ganglionic neurons. The strength and duration of reflex-induced bronchoconstriction is modulated by GABAergic-inhibitory inputs and autocrine-paracrine controlling mechanisms. Downregulation of GABAergic inhibitory influences may result in a shift from inhibitory to excitatory drive that may lead to increased excitability of AVPNs, heightened airway responsiveness, and sustained narrowing of the airways. Hence a better understanding of these normal and altered central neural circuits and mechanisms could potentially improve the design of therapeutic interventions and the treatment of airway obstructive diseases.
33
Hellysaz, Arash, and Marie Hagbom. "Understanding the Central Nervous System Symptoms of Rotavirus: A Qualitative Review." Viruses 13, no. 4 (April 11, 2021): 658. http://dx.doi.org/10.3390/v13040658.
Full textAbstract:
This qualitative review on rotavirus infection and its complications in the central nervous system (CNS) aims to understand the gut–brain mechanisms that give rise to CNS driven symptoms such as vomiting, fever, feelings of sickness, convulsions, encephalitis, and encephalopathy. There is substantial evidence to indicate the involvement of the gut–brain axis in symptoms such as vomiting and diarrhea. The underlying mechanisms are, however, not rotavirus specific, they represent evolutionarily conserved survival mechanisms for protection against pathogen entry and invasion. The reviewed studies show that rotavirus can exert effects on the CNS trough nervous gut–brain communication, via the release of mediators, such as the rotavirus enterotoxin NSP4, which stimulates neighboring enterochromaffin cells in the intestine to release serotonin and activate both enteric neurons and vagal afferents to the brain. Another route to CNS effects is presented through systemic spread via lymphatic pathways, and there are indications that rotavirus RNA can, in some cases where the blood brain barrier is weakened, enter the brain and have direct CNS effects. CNS effects can also be induced indirectly as a consequence of systemic elevation of toxins, cytokines, and/or other messenger molecules. Nevertheless, there is still no definitive or consistent evidence for the underlying mechanisms of rotavirus-induced CNS complications and more in-depth studies are required in the future.
34
Choi, Jun, Ji Kim, Jin Park, Mi Lee, Bo Song, Ji Park, Mi Kang, et al. "The Anti-Inflammatory Effects of Fermented Herbal Roots of Asparagus cochinchinensis in an Ovalbumin-Induced Asthma Model." Journal of Clinical Medicine 7, no. 10 (October 22, 2018): 377. http://dx.doi.org/10.3390/jcm7100377.
Full textAbstract:
Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.
35
Basso, Lilian, Reem Aboushousha, Churmy Yong Fan, Mircea Iftinca, Helvira Melo, Robyn Flynn, Francina Agosti, et al. "TRPV1 promotes opioid analgesia during inflammation." Science Signaling 12, no. 575 (April 2, 2019): eaav0711. http://dx.doi.org/10.1126/scisignal.aav0711.
Full textAbstract:
Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute inflammation in humans or mice enhances the analgesic properties of opioids, there is much interest in determining the inflammatory transducers that prime opioid receptor signaling in primary afferent nociceptors. Here, we found that activation of the transient receptor potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) signaling pathway that was accompanied by the shuttling of the scaffold protein β-arrestin2 to the nucleus. The nuclear translocation of β-arrestin2 in turn prevented its recruitment to the μ-opioid receptor (MOR), the subsequent internalization of agonist-bound MOR, and the suppression of MOR activity that occurs upon receptor desensitization. Using the complete Freund’s adjuvant (CFA) inflammatory pain model to examine the role of TRPV1 in regulating endogenous opioid analgesia in mice, we found that naloxone methiodide (Nal-M), a peripherally restricted, nonselective, and competitive opioid receptor antagonist, slowed the recovery from CFA-induced hypersensitivity in wild-type, but not TRPV1-deficient, mice. Furthermore, we showed that inflammation prolonged morphine-induced antinociception in a mouse model of opioid receptor desensitization, a process that depended on TRPV1. Together, our data reveal a TRPV1-mediated signaling pathway that serves as an endogenous pain-resolution mechanism by promoting the nuclear translocation of β-arrestin2 to minimize MOR desensitization. This previously uncharacterized mechanism may underlie the peripheral opioid control of inflammatory pain. Dysregulation of the TRPV1–β-arrestin2 axis may thus contribute to the transition from acute to chronic pain.
36
Thi Mai Nguyen, Huong, Der-Yen Lee, Hung-Ming Wu, and Ching-Liang Hsieh. "Auricular Acupuncture to Lower Blood Pressure Involves the Adrenal Gland in Spontaneously Hypertensive Rats." Evidence-Based Complementary and Alternative Medicine 2020 (November 20, 2020): 1–10. http://dx.doi.org/10.1155/2020/3720184.
Full textAbstract:
Auricular acupuncture is used to treat cardiac-related diseases such as hypertension. Therefore, the purpose of the present study was to investigate the effects of auricular acupuncture on blood pressure (BP) in spontaneously hypertensive rats (SHRs). The treatment group (TG) received auricular electroacupuncture (EA) at the auricle heart (CO15) and auricle shenmen (TEF3) points. Heart rate (HR) and BP, GABA-A expression, catecholamine, and neurotransmitter levels were measured. The HR was reduced after 7 auricular EA treatments compared with controls (all p < 0.05 ). Systolic BP and diastolic BP also decreased immediately and throughout the treatments compared with controls (all p < 0.05 ). The reduction of BP and HR was reversed by bicuculline injection 30 min before auricular EA treatment (all p < 0.05 ). GABA levels in the adrenal gland were higher with auricular EA treatment compared with the control group at 4 h ( p < 0.05 ). Levels of serum noradrenaline and adrenaline were reduced at 15 min after final auricular EA treatment compared with the normal control group (both p < 0.05 ). The lowering of BP and HR by auricular EA is possibly mediated via vagal afferents from the concha to the nucleus of the solitary tract. After signal integration in the medulla oblongata, it may be transmitted through sympathetic efferent or vagal efferent or through multiple signaling pathways simultaneously to the atrionector of heart and the adrenal medulla. Further study is warranted.
37
Bielefeldt, Klaus, Ashok Tuteja, and Salman Nusrat. "Disorders of gastrointestinal hypomotility." F1000Research 5 (August 1, 2016): 1897. http://dx.doi.org/10.12688/f1000research.8658.1.
Full textAbstract:
Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.
38
Hara, M., M. Toyoda, M. Yaar, J. Bhawan, E. M. Avila, I. R. Penner, and B. A. Gilchrest. "Innervation of melanocytes in human skin." Journal of Experimental Medicine 184, no. 4 (October 1, 1996): 1385–95. http://dx.doi.org/10.1084/jem.184.4.1385.
Full textAbstract:
Communication between the nervous system and epidermal melanocytes has been suspected on the basis of their common embryologic origin and apparent parallel involvement in several disease processes, but never proven. In this study, confocal microscopic analysis of human skin sections stained with antibodies specific for melanocytes and nerve fibers showed intraepidermal nerve endings in contact with melanocytes. This intimate contact was confirmed by electron microscopy, which further demonstrated thickening of apposing plasma membranes between melanocytes and nerve fibers, similar to synaptic contacts seen in nervous tissue. Since many intraepidermal nerve fibers are afferent nerves that act in a "neurosecretory" fashion through their terminals, cultured human melanocytes were stimulated with calcitonin gene-related peptide (CGRP), substance P, or vasoactive intestinal peptide, neuropeptides known to be present in cutaneous nerves, to examine their possible functions in the epidermal melanin unit. CGRP increased DNA synthesis rate of melanocytes in a concentration- and time-dependent manner. Cell yields after 5 d were increased 25% compared with controls maintained in an otherwise optimized medium. Furthermore, stimulation by CGRP induced rapid and dose-dependent accumulation of intracellular cAMP, suggesting that the mitogenic effect is mediated by the cAMP pathway. These studies confirm and expand a single earlier report in an animal model of physical contact between melanocytes and cutaneous nerves and for the first time strongly suggest that the nervous system may exert a tonic effect on melanocytes in normal or diseased human skin.
39
Raka, Fitore, Sarah Farr, Jacalyn Kelly, Alexandra Stoianov, and Khosrow Adeli. "Metabolic control via nutrient-sensing mechanisms: role of taste receptors and the gut-brain neuroendocrine axis." American Journal of Physiology-Endocrinology and Metabolism 317, no. 4 (October 1, 2019): E559—E572. http://dx.doi.org/10.1152/ajpendo.00036.2019.
Full textAbstract:
Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases.
40
Rostand, S. G., J. D. Brunzell, R. O. Cannon, and R. G. Victor. "Cardiovascular complications in renal failure." Journal of the American Society of Nephrology 2, no. 6 (December 1991): 1053–62. http://dx.doi.org/10.1681/asn.v261053.
Full textAbstract:
Cardiovascular diseases are a leading cause of death in end-stage renal disease (ESRD) largely as a result of the progressively increasing age of ESRD patients and the broad constellation of uremia-associated factors that can adversely affect cardiac function. Hypertension, one of the leading causes of renal failure, is a major culprit in this process, causing left ventricular hypertrophy, cardiac chamber dilation, increased left ventricular wall stress, redistribution of coronary blood flow, reduced coronary artery vasodilator reserve, ischemia, myocardial fibrosis, heart failure, and arrhythmias. In addition to impairing the coronary microcirculation, hypertension may contribute to the development of atherosclerotic coronary artery disease, particularly in the presence of the many lipid abnormalities observed in ESRD. These patients have reduced high-density lipoprotein cholesterol and increased plasma triglyceride concentrations, and there is a defect in cholesterol transport. Other abnormalities that may contribute to atherosclerotic coronary artery disease in ESRD are reduced high-density lipoprotein cholesterol synthesis and reduced activity of the reverse cholesterol pathway. Treatment with fibric acids, nicotinic acids, and lovastatin may be useful in lowering cholesterol and triglyceride concentrations in some of these patients. The incidence of coronary artery disease in ESRD populations is difficult to determine. About 25 to 30% of ESRD patients with angina have no evidence of significant coronary artery disease, and an undetermined number have silent coronary disease. The presence of resting electrocardiographic abnormalities caused by hypertension or conduction defects makes it difficult to accurately diagnosis coronary artery disease in ESRD populations by noninvasive methods, including exercise testing and thallium scintigraphy with or without the use of dipyridamole. Hypotension is a frequent complication of the dialytic process. Many factors have been implicated, including autonomic neuropathy. There is no consensus on the function of the efferent limb of the sympathetic nervous system. The afferent limb (arterial baroreflex function) is felt to be impaired. Further, there may be defects in the ability of the cardiovascular system to respond to sympathetic nerve activity. Most studies of autonomic function have used indirect measurements. Studies are underway that use techniques to assess sympathetic function directly. Such experiments with microneuropathy suggest greater skeletal sympathetic muscle discharge in uremic patients than in normal patients.
41
Semenov, V. G., V. G. Tyurin, D. A. Baimukanov, E. P. Simurzina, S. G. Kondruchina, A. A. Semenov, and K. Zh Iskhan. "BODY IMMUNOPROPHYLAXIS OF PREGNANT AND NEWLY-CALVED COWS." REPORTS 335, no. 1 (February 12, 2021): 39–46. http://dx.doi.org/10.32014/2021.2518-1483.6.
Full textAbstract:
The research was performed to identify the most effective bio immunostimulant. We used PS-2 and Prevention-N-E biologicals developed on the basis of the Chuvash State Agrarian University, as well as widely used in veterinary practice - PDE and E-selenium. Injection of PS-2 and Prevention-NE preparations to dry cows at a dose of 10.0 ml three times 45-40, 25-20 and 15-10 days before calving, as well as PDE and E-selenium at a dose of 20.0 and 10.0 ml 20 days before calving, respectively, prevents postpartum diseases. The mechanism of action of the PS-2 and Prevention-N-E drugs developed and tested by us is manifested, first of all, due to the consecutive processes of macrophage activation, as a result of the action of polysaccharide corpuscles and drug components on macrophage receptors. Secondly, information from the receptors of macrophages and chemoreceptors is transmitted along the afferent pathway to the cerebral cortex, then the signals go to the hypothalamus, which leads to liberin secretion by the nuclei of the ashen tuber of the hypothalamus. Liberins, in turn, increase the release of hormones by the anterior pituitary gland - the adenohypophysis. The anterior pituitary gland releases tropic hormones: somatotropic hormone, adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, etc. These hormones are involved in metabolic processes in the body. Under the influence of preparations, in cows the time of membranes sweep was reduced, the risk of uterus subinvolution and endometritis decreased. In cows, the timing of the onset of estrus, the insemination rate, and the service period were shortened, and the conception rate increased in one estrus. In such a way, against the background of the use of biologicals with the help of nonspecific adaptive reactions, the body retains the relative constancy of the internal environment necessary for life - homeostasis, and it actively resists the adverse effects of the external environment, increasing its phylactic power. Consequently, new opportunities are opening up for the implementation of the reproductive and productive qualities of cattle due to the body immunoprophylaxis with complex biological products of a new generation.
42
Jhamandas, K. H., R. J. Boegman, and R. J. Beninger. "The 1993 Upjohn Award Lecture. Quinolinic acid induced brain neurotransmitter deficits: modulation by endogenous excitotoxin antagonists." Canadian Journal of Physiology and Pharmacology 72, no. 12 (December 1, 1994): 1473–82. http://dx.doi.org/10.1139/y94-213.
Full textAbstract:
Excitotoxins constitute a group of agents that are capable of activating excitatory amino acid receptors and producing axon-sparing neuronal lesions. Focal injections of the exogenous excitotoxins kainic acid and ibotenic acid result in depletion of neurotransmitter markers in neuronal cell bodies located in areas of injection or in terminal zones of their projections. The discovery of endogenous agents that behave as excitotoxins has generated interest in the idea that excitotoxicity may contribute to the neuronal degeneration associated with a number of neurological diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) which involve selective neurotransmitter deficits. Quinolinic acid (QUIN), a pyridine dicarboxylic acid and metabolite of tryptophan, which has been detected in the central nervous system (CNS), behaves as an excitotoxin. In the mammalian brain QUIN has been localized to glial and immune cells, and its content increases with age. The neuro-excitatory and neurotoxic actions of QUIN are mediated via the Mg2+-sensitive N-methyl-D-aspartate (NMDA) receptor. The toxicity of QUIN, like that of kainate, but not ibotenate, is dependent on the presence of an intact glutamate–aspartate afferent input to the target area. Focal injections of QUIN into the nucleus basalis magnocellularis (nbM), a major source of cholinergic innervation to diencephalic areas, produce sustained loss of cholinergic neuron markers in the neocortex and amygdala. The neurotoxic action of QUIN on nbM results in an impairment of performance on memory-related tasks. Cortical and amygdaloid projecting cholinergic neurons show differential sensitivity to QUIN and other excitotoxic agents. This factor may partly explain the reported discrepancy between mnemonic deficits and the loss of cholinergic markers in the cerebral cortex induced by intra-nbM injections of certain excitotoxins. Cortical muscarinic receptor function is not significantly influenced by QUIN injections into the nbM producing loss of cortical cholinergic neurons. In the striatum, focal QUIN injections have been found to largely replicate the neurotransmitter deficits prevailing in Huntington's disease, an inherited movement disorder. Intrastriatal QUIN produces a profound loss of the NADPH diaphorase staining neurons in the area of injection but relatively spares these in the adjacent transition zone. QUIN is also highly damaging to the striatopallidal enkephalinergic neurons. However, at doses that are neurotoxic to striatal neurons, QUIN and several other excitotoxins produce significant elevations in enkephalin levels both in the striatum and globus pallidus. This elevation reflects the presence of a plasticity in the striatal enkephalinergic neuron population. The metabolic pathway yielding QUIN produces a number of intermediates that act as excitotoxin antagonists. Kynurenic acid, the most potent of these endogenous agents, blocks the action of QUIN and other excitotoxins that act on NMDA and non-NMDA receptors. Picolinic acid, a pyridine monocarboxylic acid, also attenuates QUIN toxicity. However, it only influences excitotoxins that require an intact glutamatergic afferent input to the target area for the expression of their neurotoxic action. Although picolinic acid modulates presynaptic glutamate release in vitro, this action does not entirely explain its restricted anti-excitotoxic action. The presence of several endogenous excitotoxin antagonists in the CNS has important implications for neuron survival. A balance between endogenous excitotoxins and their built-in antagonists may influence the viability of neuronal groups in the CNS. It also suggests a novel strategy for influencing excitotoxicity through elevations in levels of endogenous antagonists. Nicotinylalanine, an enzyme inhibitor, elevates brain kynurenate levels and exhibits potential for anticonvulsant and anti-excitotoxic action. The study of QUIN and related agents holds promise of understanding factors that underlie neuronal damage and developing novel agents to reduce or prevent this damage in areas of the CNS affected in neurodegenerative disease.Key words: quinolinic acid, brain, neurotransmitters, deficits, excitotoxin, antagonists.
43
You, Xin-yu, Han-yu Zhang, Xu Han, Fang Wang, Peng-wei Zhuang, and Yan-jun Zhang. "Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay." Frontiers in Pharmacology 12 (May 31, 2021). http://dx.doi.org/10.3389/fphar.2021.659716.
Full textAbstract:
Inflammatory bowel disease, irritable bowel syndrome and severe central nervous system injury can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases. Hence, repairing the intestinal barrier represents a potential therapeutic target for many diseases. Enteral afferent nerves, efferent nerves and the intrinsic enteric nervous system (ENS) play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors. In addition, intestinal microorganisms and their metabolites play a regulatory role in the intestinal mucosal barrier. This paper primarily discusses the interactions between norepinephrine and β-adrenergic receptors, cholinergic anti-inflammatory pathways, nociceptive receptors, complex ENS networks, gut microbes and various immune cells with their secreted cytokines to summarize the key roles in regulating intestinal inflammation and improving mucosal barrier function.
44
Gehrlach, Daniel A., Caroline Weiand, Thomas N. Gaitanos, Eunjae Cho, Alexandra S. Klein, Alexandru A. Hennrich, Karl-Klaus Conzelmann, and Nadine Gogolla. "A whole-brain connectivity map of mouse insular cortex." eLife 9 (September 17, 2020). http://dx.doi.org/10.7554/elife.55585.
Full textAbstract:
The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type-specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly bidirectional, the IC connectivity with subcortical structures was often unidirectional, revealing prominent cortical-to-subcortical or subcortical-to-cortical pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.
45
Bonaz, Bruno, Valérie Sinniger, and Sonia Pellissier. "Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases." Frontiers in Neuroscience 15 (March 22, 2021). http://dx.doi.org/10.3389/fnins.2021.650971.
Full textAbstract:
The vagus nerve is a mixed nerve, comprising 80% afferent fibers and 20% efferent fibers. It allows a bidirectional communication between the central nervous system and the digestive tract. It has a dual anti-inflammatory properties via activation of the hypothalamic pituitary adrenal axis, by its afferents, but also through a vago-vagal inflammatory reflex involving an afferent (vagal) and an efferent (vagal) arm, called the cholinergic anti-inflammatory pathway. Indeed, the release of acetylcholine at the end of its efferent fibers is able to inhibit the release of tumor necrosis factor (TNF) alpha by macrophages via an interneuron of the enteric nervous system synapsing between the efferent vagal endings and the macrophages and releasing acetylcholine. The vagus nerve also synapses with the splenic sympathetic nerve to inhibit the release of TNF-alpha by splenic macrophages. It can also activate the spinal sympathetic system after central integration of its afferents. This anti-TNF-alpha effect of the vagus nerve can be used in the treatment of chronic inflammatory bowel diseases, represented by Crohn’s disease and ulcerative colitis where this cytokine plays a key role. Bioelectronic medicine, via vagus nerve stimulation, may have an interest in this non-drug therapeutic approach as an alternative to conventional anti-TNF-alpha drugs, which are not devoid of side effects feared by patients.
46
Falvey, Aidan, Fabrice Duprat, Thomas Simon, Sandrine Hugues-Ascery, Silvia V. Conde, Nicolas Glaichenhaus, and Philippe Blancou. "Electrostimulation of the carotid sinus nerve in mice attenuates inflammation via glucocorticoid receptor on myeloid immune cells." Journal of Neuroinflammation 17, no. 1 (December 2020). http://dx.doi.org/10.1186/s12974-020-02016-8.
Full textAbstract:
Abstract Background The carotid bodies and baroreceptors are sensors capable of detecting various physiological parameters that signal to the brain via the afferent carotid sinus nerve for physiological adjustment by efferent pathways. Because receptors for inflammatory mediators are expressed by these sensors, we and others have hypothesised they could detect changes in pro-inflammatory cytokine blood levels and eventually trigger an anti-inflammatory reflex. Methods To test this hypothesis, we surgically isolated the carotid sinus nerve and implanted an electrode, which could deliver an electrical stimulation package prior and following a lipopolysaccharide injection. Subsequently, 90 min later, blood was extracted, and cytokine levels were analysed. Results Here, we found that carotid sinus nerve electrical stimulation inhibited lipopolysaccharide-induced tumour necrosis factor production in both anaesthetised and non-anaesthetised conscious mice. The anti-inflammatory effect of carotid sinus nerve electrical stimulation was so potent that it protected conscious mice from endotoxaemic shock-induced death. In contrast to the mechanisms underlying the well-described vagal anti-inflammatory reflex, this phenomenon does not depend on signalling through the autonomic nervous system. Rather, the inhibition of lipopolysaccharide-induced tumour necrosis factor production by carotid sinus nerve electrical stimulation is abolished by surgical removal of the adrenal glands, by treatment with the glucocorticoid receptor antagonist mifepristone or by genetic inactivation of the glucocorticoid gene in myeloid cells. Further, carotid sinus nerve electrical stimulation increases the spontaneous discharge activity of the hypothalamic paraventricular nucleus leading to enhanced production of corticosterone. Conclusion Carotid sinus nerve electrostimulation attenuates inflammation and protects against lipopolysaccharide-induced endotoxaemic shock via increased corticosterone acting on the glucocorticoid receptor of myeloid immune cells. These results provide a rationale for the use of carotid sinus nerve electrostimulation as a therapeutic approach for immune-mediated inflammatory diseases.
47
Berthoud, Hans-Rudolf, Christopher D. Morrison, Karen Ackroff, and Anthony Sclafani. "Learning of food preferences: mechanisms and implications for obesity & metabolic diseases." International Journal of Obesity, July 6, 2021. http://dx.doi.org/10.1038/s41366-021-00894-3.
Full textAbstract:
AbstractOmnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut–brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.
48
von Molitor, Elena, Katja Riedel, Michael Krohn, Mathias Hafner, Rüdiger Rudolf, and Tiziana Cesetti. "Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation." Frontiers in Human Neuroscience 15 (June 22, 2021). http://dx.doi.org/10.3389/fnhum.2021.667709.
Full textAbstract:
Sweetness is the preferred taste of humans and many animals, likely because sugars are a primary source of energy. In many mammals, sweet compounds are sensed in the tongue by the gustatory organ, the taste buds. Here, a group of taste bud cells expresses a canonical sweet taste receptor, whose activation induces Ca2+ rise, cell depolarization and ATP release to communicate with afferent gustatory nerves. The discovery of the sweet taste receptor, 20 years ago, was a milestone in the understanding of sweet signal transduction and is described here from a historical perspective. Our review briefly summarizes the major findings of the canonical sweet taste pathway, and then focuses on molecular details, about the related downstream signaling, that are still elusive or have been neglected. In this context, we discuss evidence supporting the existence of an alternative pathway, independent of the sweet taste receptor, to sense sugars and its proposed role in glucose homeostasis. Further, given that sweet taste receptor expression has been reported in many other organs, the physiological role of these extraoral receptors is addressed. Finally, and along these lines, we expand on the multiple direct and indirect effects of sugars on the brain. In summary, the review tries to stimulate a comprehensive understanding of how sweet compounds signal to the brain upon taste bud cells activation, and how this gustatory process is integrated with gastro-intestinal sugar sensing to create a hedonic and metabolic representation of sugars, which finally drives our behavior. Understanding of this is indeed a crucial step in developing new strategies to prevent obesity and associated diseases.
49
Parodi, Benedetta, and Nicole Kerlero de Rosbo. "The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?" Frontiers in Immunology 12 (September 21, 2021). http://dx.doi.org/10.3389/fimmu.2021.718220.
Full textAbstract:
A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.
50
Crisafulli, Ernesto, and Enrico M. Clini. "Measures of dyspnea in pulmonary rehabilitation." Multidisciplinary Respiratory Medicine 5 (August 22, 2010). http://dx.doi.org/10.4081/mrm.2010.529.
Full textAbstract:
Dyspnea is the main symptom perceived by patients affected by chronic respiratory diseases. It derives from a complex interaction of signals arising in the central nervous system, which is connected through afferent pathway receptors to the peripheral respiratory system (airways, lung, and thorax). Notwithstanding the mechanism that generates the stimulus is always the same, the sensation of dyspnea is often described with different verbal descriptors: these descriptors, or linguistic ‘clusters’, are clearly influenced by socio-individ- ual factors related to the patient. These factors can play an important role in identifying the etiopathogenesis of the underlying cardiopulmonary disease causing dyspnea.
The main goal of rehabilitation is to improve dyspnea; hence, quantifying dyspnea through specific tools (scales) is essen- tial in order to describe the level of chronic disability and to assess eventual changes after intervention. Improvements, even if modest, are likely to determine clinically relevant changes (minimal clinically important difference, MCID) in patients.
Currently there exist a large number of scales to classify and characterize dyspnea: the most frequently used in everyday clinical practice are the clinical scales (e.g. MRC or BDI/TDI, in which information is obtained directly from the patients through interview) and psychophysical scales (such as the Borg scale or VAS, which assess symptom intensity in response to a specific stimulus, e.g. exercise). It is also possible to assess the individual’s dyspnea in rela- tion to specific situations, e.g. chronic dyspnea (with scales that classify patients according to different levels of respira- tory disability); exertional dyspnea (with tools that can measure the level of dyspnea in response to a physical stim- ulus); and transitional (or ‘follow up’) dyspnea (with scales that measure the effect in time of a treatment intervention, such as rehabilitation).