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American Journal of Physiology.... Sep 2017A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans. The aims of this study were to...
A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans. The aims of this study were to determine whether animals have an SGB and, if so, to determine its mechanisms. Studies were conducted in decerebrate cats ( = 30) with electromyographic electrodes on hyoid, pharyngeal, esophageal, and diaphragm muscles. The effects of distending different regions of the esophagus in different manners using a balloon were quantified to determine the most appropriate stimulus for activating the cat SGB. The effects of esophageal perfusion of lidocaine ( = 3), vagus nerve transection ( = 3), or esophageal acidification ( = 5) on activation of the SGB were determined. Rapid large distensions of the thoracic esophagus best activated responses similar to the human SGB, i.e., rapid inhalation followed by a belch. The rapid inhalation was associated with activation of hiatal fibers and the belch with activation of dome fibers of the diaphragm. The rapid inhalation response was independent of the belch response. Lidocaine perfusion of the esophagus blocked the belch response without blocking the rapid inhalation, HCl perfusion sensitized the esophagus to activation of both the rapid inhalation and the belch response, and vagotomy blocked both responses. We conclude that the cat has an SGB that is composed of two independent reflex responses, i.e., rapid inhalation and belch, that are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. We hypothesize that the SGB is a learned voluntarily activated reflex response. Rapid strong distension of the thoracic esophagus activates rapid inhalation followed by a belch, which is the sequence of responses that compose the human supragastric belch (SGB). The rapid inhalation and belch phases of the cat SGB are activated by hiatal and dome fibers of the diaphragm, respectively, and are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. There are many similarities between the cat and human SGB.
Topics: Anesthetics, Local; Animals; Cats; Eructation; Esophagus; Hydrochloric Acid; Hydrogen-Ion Concentration; Lidocaine; Vagotomy
PubMed: 28619729
DOI: 10.1152/ajpgi.00142.2017 -
Journal of Oncology 2018This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the... (Review)
Review
This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the relationship between heart rate variability, the main vagus nerve index, and prognosis in cancer patients (survival and tumor markers). These studies show that initially high vagal nerve activity predicts better cancer prognosis, and, in some studies, independent of confounders such as cancer stage and treatments. Since the design of the epidemiological studies is correlational, any causal relationship between heart rate variability and cancer prognosis cannot be inferred. However, various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship. The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth, while vagal nerve activation improves cancer prognosis. Based on all reviewed studies, it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage.
PubMed: 30057605
DOI: 10.1155/2018/1236787 -
Neurobiology of Disease Jan 2023Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination...
Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling that of patients with MS. Given the role of the vagus nerve in gut-microbiota-brain axis in development of MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects demyelination in CPZ-treated mice. SDV significantly ameliorated demyelination and microglial activation in the brain compared with sham-operated CPZ-treated mice. Furthermore, 16S ribosomal RNA analysis revealed that SDV significantly improved the abnormal gut microbiota composition of CPZ-treated mice. An untargeted metabolomic analysis demonstrated that SDV significantly improved abnormal blood levels of metabolites in CPZ-treated mice compared with sham-operated CPZ-treated mice. Notably, there were correlations between demyelination or microglial activation in the brain and the relative abundance of several microbiome populations, suggesting a link between gut microbiota and the brain. There were also correlations between demyelination or microglial activation in the brain and blood levels of metabolites. Together, these data suggest that CPZ produces demyelination in the brain through the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve.
Topics: Animals; Mice; Brain; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Mice, Inbred C57BL; Microbiota; Microglia; Multiple Sclerosis; Vagus Nerve
PubMed: 36493975
DOI: 10.1016/j.nbd.2022.105951 -
Journal of Medicine and Life 2016Gastric stump cancer (GSC) is the malignant tumor that develops in the gastric remnant after partial gastrectomy was performed both for benign and malignant lesions.... (Review)
Review
Gastric stump cancer (GSC) is the malignant tumor that develops in the gastric remnant after partial gastrectomy was performed both for benign and malignant lesions. This paper presents the results of the case studies from the scientific literature, which focused on GSC, and has been published in the last 10 years. The search was performed with the help of the specific tools offered by the international databases. The subject was approached because of the constant rising incidence of GSC in the past few years, now reaching values between 1% and 7%. The outcome report is consistent and similar to the period that ended approximately 25 years ago, when general surgeons dedicated a significant part of their activity to treating gastric ulcer. Statistics revealed that the main risk factors are the following: the type of reconstruction after distal gastrectomy (Billroth I or Billroth II), the presence of duodenogastric reflux, the time between gastric resections, and the moment of diagnosis of gastric stump cancer, the initial pathology for which partial gastrectomy was performed, gender, age, helicobacter pylori infection, Epstein Barr virus infection and the presence of vagotomy. All the authors have significantly contributed to the article and have been involved in the writing of the manuscript in draft and any revision stages, and have read and approved the final version.
Topics: Adult; Age Factors; Aged; Duodenogastric Reflux; Female; Gastrectomy; Gastric Stump; Helicobacter Infections; Humans; Male; Middle Aged; Risk Factors; Sex Factors; Stomach Neoplasms
PubMed: 27453741
DOI: No ID Found -
Journal of Dairy Science Mar 2023Conceptual models developed over the past century describe 2 key constraints to feed intake (FI) of healthy animals: gut capacity and metabolic demand. Evidence that... (Review)
Review
Conceptual models developed over the past century describe 2 key constraints to feed intake (FI) of healthy animals: gut capacity and metabolic demand. Evidence that greater energy demands (e.g., greater milk production) drive a corresponding increase in caloric intake led to the dominant concept that animals "eat to energy requirements." Although this model provides reasonable initial estimates of FI, it lacks a proposed physiological basis for the control system, does not consider nutrient constraints beyond energy, and fails to explain differential energy intake responses to different fuels. To address these gaps, research has focused on mechanisms for sensing nutrient availability and providing feedback to hypothalamic centers that integrate signals to control feeding behavior. The elimination of FI response to certain nutrients by vagotomy suggests that peripheral tissues play a role in nutrient sensing. These findings and the central role of the liver in metabolic flux led to the development of the hepatic oxidation theory (HOT). According to the HOT, liver energy charge is the regulated variable that induces dietary intake changes and consequently affects whole-body energy balance. Evidence in support of HOT includes associations between hepatic energy charge and meal patterns, increased FI in response to phosphate trapping, and reduced FI in response to phosphate loading. In accordance with the HOT, infusion studies in dairy cattle have consistently demonstrated that providing fuels that either oxidize or stimulate oxidation in the liver decreases FI and energy intake to a greater extent than fuels that bypass the liver. Importantly, this holds true for glucose, which is readily oxidized by nerve cells, but is rarely taken up by the bovine liver. Although the brain integrates multiple signals including those related to gastric distention and illness, the HOT provides a physiological framework for understanding the dominant role the liver likely plays in sensing short-term energy status. Understanding this model provides insights into how to use or bypass the regulatory system to manage FI of animals.
Topics: Cattle; Animals; Appetite; Eating; Feeding Behavior; Energy Intake; Energy Metabolism; Nutrients
PubMed: 36543641
DOI: 10.3168/jds.2022-22429 -
Scientific Reports Jun 2020Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits....
Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits. Selective activation of afferent or efferent vagal fibers can maximize efficacy and minimize off-target effects of VNS. Anodal block (ABL) has been used to achieve directional fiber activation in nerve stimulation. However, evidence for directional VNS with ABL has been scarce and inconsistent, and it is unknown whether ABL permits directional fiber activation with respect to functional effects of VNS. Through a series of vagotomies, we established physiological markers for afferent and efferent fiber activation by VNS: stimulus-elicited change in breathing rate (ΔBR) and heart rate (ΔHR), respectively. Bipolar VNS trains of both polarities elicited mixed ΔHR and ΔBR responses. Cathode cephalad polarity caused an afferent pattern of responses (relatively stronger ΔBR) whereas cathode caudad caused an efferent pattern (stronger ΔHR). Additionally, left VNS elicited a greater afferent and right VNS a greater efferent response. By analyzing stimulus-evoked compound nerve potentials, we confirmed that such polarity differences in functional responses to VNS can be explained by ABL of A- and B-fiber activation. We conclude that ABL is a mechanism that can be leveraged for directional VNS.
Topics: Action Potentials; Animals; Electrocardiography; Electrodes, Implanted; Heart Rate; Male; Rats; Rats, Sprague-Dawley; Respiratory Rate; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 32513973
DOI: 10.1038/s41598-020-66332-y -
PloS One 2019GPR40/FFAR1 is a Gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding...
GPR40/FFAR1 is a Gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding behavior. Several GPR40 full agonists have been reported to reduce food intake in rodents by regulating gut hormone secretion in addition to their potent glucose-lowering effects; however, detailed mechanisms of feeding suppression are still unknown. In the present study, we characterized T-3601386, a novel compound with potent full agonistic activity for GPR40, by using in vitro Ca2+ mobilization assay in Chinese hamster ovary (CHO) cells expressing FFAR1 and in vivo hormone secretion assay. We also evaluated feeding suppression and weight loss after the administration of T-3601386 and investigated the involvement of the vagal nerve in these effects. T-3601386, but not a partial agonist fasiglifam, increased intracellular Ca2+ levels in CHO cells with low FFAR1 expression, and single dosing of T-3601386 in diet-induced obese (DIO) rats elevated plasma incretin levels, suggesting full agonistic properties of T-3601386 against GPR40. Multiple doses of T-3601386, but not fasiglifam, in DIO rats showed dose-dependent weight loss accompanied by feeding suppression and durable glucagon-like peptide-1 elevation, all of which were completely abolished in Ffar1-/- mice. Immunohistochemical analysis in the nuclei of the solitary tract demonstrated that T-3601386 increased the number of c-Fos positive cells, which also disappeared in Ffar1-/- mice. Surgical vagotomy and drug-induced deafferentation counteracted the feeding suppression and weight loss induced by the administration of T-3601386. These results suggest that T-3601386 exerts incretin release and weight loss in a GPR40-dependent manner, and that afferent vagal nerves are important for the feeding suppression induced by GPR40 full agonism. Our novel findings raise the possibility that GPR40 full agonist can induce periphery-derived weight reduction, which may provide benefits such as less adverse effects in central nervous system compared to centrally-acting anti-obesity drugs.
Topics: Animals; Blood Glucose; CHO Cells; Calcium; Cell Line; Cricetulus; Enteroendocrine Cells; Female; Glucagon-Like Peptide 1; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Male; Mice; Obesity; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Rats, Wistar; Receptors, G-Protein-Coupled; Signal Transduction; Vagus Nerve; Weight Loss
PubMed: 31525244
DOI: 10.1371/journal.pone.0222653 -
Biomedicines Apr 2023GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body...
GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.
PubMed: 37238993
DOI: 10.3390/biomedicines11051322 -
International Journal of Molecular... Nov 2018Parkinson's disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects' research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.
Topics: Animals; Brain; Disease Models, Animal; Gastrointestinal Diseases; Humans; Parkinson Disease; Prion Diseases; alpha-Synuclein
PubMed: 30424585
DOI: 10.3390/ijms19113573 -
Virulence Dec 2021Abnormalities in CD4 T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that...
Abnormalities in CD4 T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve's effect on differentiation of CD4 T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4 T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4 T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4 T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4 T cells. The CD4 T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4 T cell differentiation in response to VMC.
Topics: Acute Disease; Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Coxsackievirus Infections; Cytokines; Enterovirus B, Human; Male; Mice; Mice, Inbred BALB C; Myocarditis; Vagus Nerve
PubMed: 33380272
DOI: 10.1080/21505594.2020.1869384