Search

Nausea and vomiting are common gastrointestinal side effects of oxaliplatin chemotherapy used for the treatment of colorectal cancer. However, the mechanism underlying oxaliplatin-induced nausea and vomiting is unknown. The stomach is involved in the emetic reflex but no study investigated the effects of oxaliplatin treatment on the stomach. In this study, the in vivo effects of oxaliplatin treatment on eating behaviour, stomach content, intrinsic gastric neuronal population, extrinsic innervation to the stomach, levels of mucosal serotonin (5-hydroxytryptamine, 5-HT), and parasympathetic vagal efferent nerve activity were analysed. Chronic systemic oxaliplatin treatment in mice resulted in pica, indicated by increased kaolin consumption and a reduction in body weight. Oxaliplatin treatment significantly increased the stomach weight and content. The total number of myenteric and nitric oxide synthase-immunoreactive neurons as well as the density of sympathetic, parasympathetic, and sensory fibres in the stomach were decreased significantly with oxaliplatin treatment. Oxaliplatin treatment significantly increased the levels in mucosal 5-HT and the number of enterochromaffin-like cells. Chronic oxaliplatin treatment also caused a significant increase in the vagal efferent nerve activity. The findings of this study indicate that oxaliplatin exposure has adverse effects on multiple components of gastric innervation, which could be responsible for pica and gastric dysmotility. [ABSTRACT FROM AUTHOR]

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca 2+ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca 2+ currents were inhibited with a log (Ic 50 ) = -2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca 2+ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca 2+ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca 2+ current inhibition was mediated by the G α i/o or G α q/11 family of subunits. Treatment with both PTX (Ca 2+ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin's effects on Ca 2+ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both G α i/o and G α q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca 2+ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin's regulation of gastric vagal afferents. SIGNIFICANCE STATEMENT: This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca 2+ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Nausea and vomiting are common gastrointestinal side effects of oxaliplatin chemotherapy used for the treatment of colorectal cancer. However, the mechanism underlying oxaliplatin-induced nausea and vomiting is unknown. The stomach is involved in the emetic reflex but no study investigated the effects of oxaliplatin treatment on the stomach. In this study, the in vivo effects of oxaliplatin treatment on eating behaviour, stomach content, intrinsic gastric neuronal population, extrinsic innervation to the stomach, levels of mucosal serotonin (5-hydroxytryptamine, 5-HT), and parasympathetic vagal efferent nerve activity were analysed. Chronic systemic oxaliplatin treatment in mice resulted in pica, indicated by increased kaolin consumption and a reduction in body weight. Oxaliplatin treatment significantly increased the stomach weight and content. The total number of myenteric and nitric oxide synthase-immunoreactive neurons as well as the density of sympathetic, parasympathetic, and sensory fibres in the stomach were decreased significantly with oxaliplatin treatment. Oxaliplatin treatment significantly increased the levels in mucosal 5-HT and the number of enterochromaffin-like cells. Chronic oxaliplatin treatment also caused a significant increase in the vagal efferent nerve activity. The findings of this study indicate that oxaliplatin exposure has adverse effects on multiple components of gastric innervation, which could be responsible for pica and gastric dysmotility.

Few biomarkers support the diagnosis and treatment of disorders of gut-brain interaction (DGBI), although gastroduodenal junction (GDJ) electromechanical coupling is a target for novel interventions. Rhythmic "slow waves," generated by interstitial cells of Cajal (ICC), and myogenic "spikes" are bioelectrical mechanisms underpinning motility. In this study, simultaneous in vivo high-resolution electrophysiological and impedance planimetry measurements were paired with immunohistochemistry to elucidate GDJ electromechanical coupling. Following ethical approval, the GDJ of anaesthetized pigs ( n = 12) was exposed. Anatomically specific, high-resolution electrode arrays (256 electrodes) were applied to the serosa. EndoFLIP catheters (16 electrodes; Medtronic, MN) were positioned luminally to estimate diameter. Postmortem tissue samples were stained with Masson's trichrome and Ano1 to quantify musculature and ICC. Electrical mapping captured slow waves ( n = 512) and spikes ( n = 1,071). Contractions paralleled electrical patterns. Localized slow waves and spikes preceded rhythmic contractions of the antrum and nonrhythmic contractions of the duodenum. Slow-wave and spike amplitudes were correlated in the antrum ( r = 0.74, P < 0.001) and duodenum ( r = 0.42, P < 0.001). Slow-wave and contractile amplitudes were correlated in the antrum ( r = 0.48, P < 0.001) and duodenum ( r = 0.35, P < 0.001). Distinct longitudinal and circular muscle layers of the antrum and duodenum had a total thickness of (2.8 ± 0.9) mm and (0.4 ± 0.1) mm, respectively. At the pylorus, muscle layers merged and thickened to (3.5 ± 1.6) mm. Pyloric myenteric ICC covered less area (1.5 ± 1.1%) compared with the antrum (4.2 ± 3.0%) and duodenum (5.3 ± 2.8%). Further characterization of electromechanical coupling and ICC biopsies may generate DGBI biomarkers. NEW & NOTEWORTHY This study applies electrical mapping, impedance planimetry, and histological techniques to the gastroduodenal junction to elucidate electromechanical coupling in vivo. Contractions of the terminal antrum and pyloric sphincter were associated with gastric slow waves. In the duodenum, bursts of spike activity triggered oscillating contractions. The relative sparsity of myenteric interstitial cells of Cajal in the pylorus, compared with the adjacent antrum and duodenum, is hypothesized to prevent coupling between antral and duodenal slow waves.

The influence of accelerated electrons on neuronal structures is scarcely explored compared to gamma and X-rays. This study aims to investigate the effects of accelerated electron radiation on some pivotal neurotransmitter circuits (cholinergic and serotonergic) of rats' myenteric plexus. Male Wistar rats were irradiated with an electron beam (9 MeV, 5 Gy) generated by a multimodality linear accelerator. The contractile activity of isolated smooth muscle samples from the gastric corpus was measured. Furthermore, an electrical stimulation (200 μs, 20 Hz, 50 s, 60 V) was performed on the samples and an assessment of the cholinergic and serotonergic circuits was made. Five days after irradiation, the recorded mechanical responses were biphasic-contraction/relaxation in controls and contraction/contraction in irradiated samples. The nature of the contractile phase of control samples was cholinergic with serotonin involvement. The relaxation phase involved ACh-induced nitric oxide release from gastric neurons. There was a significant increase in serotonergic involvement during the first and second contractile phases of the irradiated samples, along with a diminished role of acetylcholine in the first phase. This study demonstrates an increased involvement of serotonergic neurotransmitter circuits in the gastric myenteric plexus caused by radiation with accelerated electrons.

Objective: There has been recent clinical interest in the use of vagus nerve stimulation (VNS) for treating gastrointestinal disorders as an alternative to drugs or gastric electrical stimulation. However, effectiveness of burst stimulation has not been demonstrated. We investigated the ability of bursting and continuous VNS to influence gastric and pyloric activity under a range of stimulation parameters and gastric pressures. The goals of this study were to determine which parameters could optimally excite or inhibit gastric activity., Materials and Methods: Data were collected from 21 Sprague-Dawley rats. Under urethane anesthesia, a rubber balloon was implanted into the stomach, connected to a pressure transducer and a saline infusion pump. A pressure catheter was inserted at the pyloric sphincter and a bipolar nerve cuff was implanted onto the left cervical vagus nerve. The balloon was filled to 15 cmH 2 O. Stimulation trials were conducted in a consistent order; the protocol was then repeated at 25 and 35 cmH 2 O. The nerve was then transected and stimulation repeated to investigate directionality of effects., Results: Bursting stimulation at the bradycardia threshold caused significant increases in gastric contraction amplitude with entrainment to the bursting frequency. Some continuous stimulation trials could also cause increased contractions but without frequency changes. Few significant changes were observed at the pylorus, except for frequency entrainment. These effects could not be uniquely attributed to afferent or efferent activity., Significance: Our findings further elucidate the effects of different VNS parameters on the stomach and pylorus and provide a basis for future studies of bursting stimulation for gastric neuromodulation., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: The effects of gastric electrical stimulation are not fully understood. We aimed to assess the efficacy of gastric electrical stimulation (GES) for patients with gastroparesis and gastroparesis-like symptoms., Materials and Methods: We searched PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct to identify controlled trials and cohort studies. We used random effects models to estimate pooled effects. A total of nine studies met the criteria and were included for the final qualitative synthesis and the quantitative analysis. We examined the mean absolute differences (MD) and 95% CIs., Results: Nine studies (n = 730) met the criteria and were included for the final qualitative synthesis and the quantitative analysis. There was significant improvement in gastrointestinal (GI) total symptom score (TSS) with the GES group compared with controls during the randomized blind trials. This effect was sustained at 12 months after treatment compared with before treatment (MD = -6.07; 95% CI, -4.5 to -7.65; p < 0.00001). The pooled effect estimate showed a significant improvement in frequency of weekly vomiting episodes at 12 months compared with before treatment (MD = -15.59; 95% CI, -10.29 to -20.9; p < 0.00001)., Conclusion: GES appears beneficial, with significant improvement in GI TSS, weekly vomiting frequency, gastric emptying study, and quality of life., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The stomach is the primary reservoir of the gastrointestinal tract, where ingested content is broken down into small particles. Coordinated relaxation and contraction is essential for rhythmic motility and digestion, but how the muscle motor innervation is organized to provide appropriate graded regional control is not established. In this study, we recorded neuromuscular transmission to the circular muscle using intracellular microelectrodes to investigate the spread of the influence of intrinsic motor neurons. In addition, microanatomical investigations of neuronal projections and pharmacological analysis were conducted to investigate neuromuscular relationships. We found that inhibitory neurotransmission to the circular muscle is graded with stimulus strength and circumferential distance from the stimulation site. The influence of inhibitory neurons declined between 1 and 11 mm from the stimulation site. In the antrum, corpus, and fundus, the declines at 11 mm were about 20%, 30%, and 50%, respectively. Stimulation of inhibitory neurons elicited biphasic hyperpolarizing potentials often followed by prolonged depolarizing events in the distal stomach, but only hyperpolarizing events in the proximal stomach. Excitatory neurotransmission influence varied greatly between proximal stomach, where depolarizing events occurred, and distal stomach, where no direct electrical effects in the muscle were observed. Structural studies using microlesion surgeries confirmed a dominant circumferential projection. We conclude that motor neuron influences extend around the gastric circumference, that the effectiveness can be graded by the recruitment of different numbers of motor neuron nerve terminals to finely control gastric motility, and that the ways in which the neurons influence the muscle differ between anatomical regions. NEW & NOTEWORTHY This study provides a detailed mapping of nerve transmission to the circular muscle of the different anatomical regions of rat stomach. It shows that excitatory and inhibitory influences extend around the gastric circumference and that there is a summation of neural influence that allows for finely graded control of muscle tension and length. Nerve-mediated electrical events are qualitatively and quantitatively different between regions, for example, excitatory neurons have direct effects on fundus but not antral muscle.

Background: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship.Aims: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes.Methods: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) within a 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression.Results: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p < 0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p = 0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES.Conclusions: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is widely utilized in plastic production process all over the world. Previous studies have shown that BPA, with its similarity to estrogen, may negatively affect living organisms. It is acknowledged that BPA distorts the activity of multiple internal systems, including the nervous, reproductive, urinary, and endocrine systems. BPA also affects the gastrointestinal tract and enteric nervous system (ENS), which is placed throughout the wall from the esophagus to the rectum. Contrary to the intestine, the influence of BPA on the ENS in the stomach is still little known. This study, performed using the double immunofluorescence method, has revealed that BPA affects the number of nervous structures in the porcine gastric wall immunoreactive to vesicular acetylcholine transporter (VAChT, a marker of cholinergic neurons), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL) and cocaine- and amphetamine-regulated transcript peptide (CART). The character and severity of noted alterations depended on the part of the ENS, the BPA dose, and the type of neuronal substance. Administration of BPA resulted in an increase in the number of nervous structures containing SP, GAL, and/or CART, and a decrease in the number of cholinergic neurons in all parts of the gastric wall. The number of VIP-positive nervous structures increased in the enteric myenteric ganglia, along with the muscular and mucosal layers, whilst it decreased in the submucous ganglia. The exact mechanism of noted changes was not absolutely obvious, but they were probably related to the neuroprotective and adaptive processes constituting the response to the impact of BPA.

The dorsal root ganglia (DRG) project spinal afferent axons to the stomach. However, the distribution and morphology of spinal afferent axons in the stomach have not been well characterized. In this study, we used a combination of state-of-the-art techniques, including anterograde tracer injection into the left DRG T7-T11, avidin-biotin and Cuprolinic Blue labeling, Zeiss M2 Imager, and Neurolucida to characterize spinal afferent axons in flat-mounts of the whole rat stomach muscular wall. We found that spinal afferent axons innervated all regions with a variety of distinct terminal structures innervating different gastric targets: (1) The ganglionic type: some axons formed varicose contacts with individual neurons within myenteric ganglia. (2) The muscle type: most axons ran in parallel with the longitudinal and circular muscles and expressed spherical varicosities. Complex terminal structures were observed within the circular muscle layer. (3) The ganglia-muscle mixed type: some individual varicose axons innervated both myenteric neurons and the circular muscle, exhibiting polymorphic terminal structures. (4) The vascular type: individual varicose axons ran along the blood vessels and occasionally traversed the vessel wall. This work provides a foundation for future topographical anatomical and functional mapping of spinal afferent axon innervation of the stomach under normal and pathophysiological conditions., (© 2023. Springer Nature Limited.)

Background: Visceral pain is initiated by activation of primary afferent neurons among which the capsaicin-sensitive (TRPV1-positive) neurons play an important role. The stomach is a common source of visceral pain. Similar to other organs, the stomach receives dual spinal and vagal afferent innervation. Developmentally, spinal dorsal root ganglia (DRG) and vagal jugular neurons originate from embryonic neural crest and vagal nodose neurons originate from placodes. In thoracic organs the neural crest- and placodes-derived TRPV1-positive neurons have distinct phenotypes differing in activation profile, neurotrophic regulation and reflex responses. It is unknown to whether such distinction exists in the stomach.Aims: We hypothesized that gastric neural crest- and placodes-derived TRPV1-positive neurons express phenotypic markers indicative of placodes and neural crest phenotypes.Methods: Gastric DRG and vagal neurons were retrogradely traced by DiI injected into the rat stomach wall. Single-cell RT-PCR was performed on traced gastric neurons.Results: Retrograde tracing demonstrated that vagal gastric neurons locate exclusively into the nodose portion of the rat jugular/petrosal/nodose complex. Gastric DRG TRPV1-positive neurons preferentially expressed markers PPT-A, TrkA and GFRα3 typical for neural crest-derived TRPV1-positive visceral neurons. In contrast, gastric nodose TRPV1-positive neurons preferentially expressed markers P2X2 and TrkB typical for placodes-derived TRPV1-positive visceral neurons. Differential expression of neural crest and placodes markers was less pronounced in TRPV1-negative DRG and nodose populations.Conclusions: There are phenotypic distinctions between the neural crest-derived DRG and placodes-derived vagal nodose TRPV1-positive neurons innervating the rat stomach that are similar to those described in thoracic organs. [ABSTRACT FROM AUTHOR]

Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders., Competing Interests: Declaration of interests S.D.L. is a consultant for Kallyope., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bisphenol A (BPA), an organic chemical compound which is widely used in the production of plastics, can severely damage live organisms. Due to these findings, the plastic industry has started to replace it with other substances, most often with bisphenol S (BPS). Therefore, during the present investigation, with the use of double immunofluorescence labeling, we compared the effect of BPA and BPS on the enteric nervous system (ENS) in the mouse corpus of the stomach. The obtained results show that both studied toxins impact the amount of nerve cells immunoreactive to substance P (SP), galanin (GAL), vesicular acetylcholine transporter (VAChT is used here as a marker of cholinergic neurons) and vasoactive intestinal polypeptide (VIP). Changes observed under the impact of both bisphenols depended on the neuronal factor, the type of the enteric ganglion and the doses of bisphenols studied. Generally, the increase in the percentage of neurons immunoreactive to SP, GAL and/or VIP, and the decrease in the percentage of VAChT-positive neurons, was noted. Severity of changes was more visible after BPA administration. However, the study has shown that long time exposure to BPS also significantly affects the ENS.

Aims: The objective of this study was to investigate sacral electrical stimulation (SES) and gastric electrical stimulation (GES) by comparing upper and lower gastrointestinal (GI) and genitourinary (GU) symptoms and quality of life, before treatment and in the long term after treatment. We hypothesized that dual-device treatment would greatly improve upper and lower gastrointestinal and genitourinary symptoms, as well as quality of life. Methods: Fifty-four patients who underwent dual-device treatment (GES and SES) were enrolled in this study. Patients who had surpassed 24 months since the second-device insertion were included. Patients were evaluated before and after both devices were implanted and given a symptom questionnaire regarding their upper GI, lower GI, and GU symptoms and their quality of life. Results: With combined treatment, a statistically significant improvement was seen in upper GI, lower GI, and GU symptoms and quality of life. However, fecal incontinence and fecal urgency improvements did not reach statistical significance, likely due to the small sample size. Conclusion: The implantation of two stimulators appears to be safe and effective to improve patients' quality of life for those with upper GI symptoms, bowel problems, and bladder dysfunction. [ABSTRACT FROM AUTHOR]

Nociceptive afferents innervate the stomach and send signals centrally to the brain and locally to stomach tissues. Nociceptive afferents can be detected with a variety of different markers. In particular, substance P (SP) is a neuropeptide and is one of the most commonly used markers for nociceptive nerves in the somatic and visceral organs. However, the topographical distribution and morphological structure of SP-immunoreactive (SP-IR) axons and terminals in the whole stomach have not yet been fully determined. In this study, we labeled SP-IR axons and terminals in flat mounts of the ventral and dorsal halves of the stomach of mice. Flat-mount stomachs, including the longitudinal and circular muscular layers and the myenteric ganglionic plexus, were processed with SP primary antibody followed by fluorescent secondary antibody and then scanned using confocal microscopy. We found that (1) SP-IR axons and terminals formed an extensive network of fibers in the muscular layers and within the ganglia of the myenteric plexus of the whole stomach. (2) Many axons that ran in parallel with the long axes of the longitudinal and circular muscles were also immunoreactive for the vesicular acetylcholine transporter (VAChT). (3) SP-IR axons formed very dense terminal varicosities encircling individual neurons in the myenteric plexus; many of these were VAChT immunoreactive. (4) The regional density of SP-IR axons and terminals in the muscle and myenteric plexus varied in the following order from high to low: antrum-pylorus, corpus, fundus, and cardia. (5) In only the longitudinal and circular muscles, the regional density of SP-IR axon innervation from high to low were: antrum-pylorus, corpus, cardia, and fundus. (6) The innervation patterns of SP-IR axons and terminals in the ventral and dorsal stomach were comparable. Collectively, our data provide for the first time a map of the distribution and morphology of SP-IR axons and terminals in the whole stomach with single-cell/axon/synapse resolution. This work will establish an anatomical foundation for functional mapping of the SP-IR axon innervation of the stomach and its pathological remodeling in gastrointestinal diseases., (© 2022 Wiley Periodicals LLC.)

Interneuronal transfer of pathological α-synuclein species is thought to play an important role in the progressive advancement of Lewy pathology and increasing severity of clinical manifestations in Parkinson's and other diseases commonly referred to as synucleinopathies. Pathophysiological conditions and mechanisms triggering this trans-synaptic spreading bear therefore significant pathogenetic implications but have yet to be fully elucidated. In vivo experimental models support the conclusion that increased expression of intraneuronal α-synuclein can itself induce protein spreading throughout the brain as well as from the brain to peripheral tissues. For example, overexpression of α-synuclein targeted to the rodent dorsal medulla oblongata results in its transfer and accumulation into recipient axons innervating this brain region; through these axons, α-synuclein can then travel caudo-rostrally and reach other brain sites in the pons, midbrain, and forebrain. When protein overexpression is induced in the rodent midbrain, long-distance α-synuclein spreading can be followed over time; spreading-induced α-synuclein accumulation affects lower brain regions, including the dorsal motor nucleus of the vagus, proceeds through efferent axons of the vagus nerve, and is ultimately detected within vagal motor nerve endings in the gastric wall. As discussed in this review, animal models featuring α-synuclein overexpression not only support a relationship between α-synuclein burden and protein spreading but have also provided important clues on conditions/mechanisms capable of promoting interneuronal α-synuclein transfer. Intriguing findings include the relationship between neuronal activity and protein spreading and the role of oxidant stress in trans-synaptic α-synuclein mobility., (© 2022. The Author(s).)

Background Visceral adipose tissue (VAT) is a unique pathogenic fatty deposit, in that it is closely correlated with risk of cardiovascular diseases. The present study is to investigate the usefulness of neck circumference (NC) to indicate VAT. Methods Participants aged 35 to 75 years who had taken abdomen and neck computer tomography (CT) examination were included in this study. Neck adipose tissue, abdominal VAT and subcutaneous adipose tissue (SAT) areas, as well as sagittal abdominal diameter (SAD) were measured by CT. Body anthropometrics and metabolic parameters including blood glucose, lipid profiles and blood pressure were also measured. Results A lower abdomen CT examination was carried out on a total of 177 patients (87 male and 90 female) with a mean age of 59 years. Of the 177 participants, 15 men and 15 women also took a neck CT examination. With a comparable age and BMI, neck adipose area was correlated with abdominal VAT area significantly in men (r = 0.57, p = 0.028) and women (r = 0.53, p = 0.041). NC is positively correlated with VAT both in men (r = 0.49, p < 0.001) and women (r = 0.25, p = 0.012). Meanwhile, SAD is the best predictor for visceral fat both in men (r = 0.83, p < 0.001) and women (r = 0.73, p < 0.001). Body mass index (BMI), waist circumference (WC), and waist to height ratio (WHtR) correlated significantly with VAT both in men and women (r = 0.68, 0.42, 0.46 in men and 0.50, 0.23, 0.39 in women, p < 0.001), while waist hip ratio (WHR) displayed the weakest least correlation in men (r = 0.32, p = 0.001) and no correlation in women (r = 0.08, p = 0.442). Additionally, BMI was more strongly correlated with VAT than NC in both sexes (both p < 0.01). Conclusion Significant correlation between NC and VAT was present in Chinese men and women, which may be accounted by the fact that neck fat area is significantly correlated with abdominal VAT. Meanwhile, SAD is the best predictor for visceral fat in the Chinese population. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) is a signal peptide released from enteroendocrine cells of the lower intestine. GLP-1 exerts anorectic and antimotility actions that protect the body against nutrient malabsorption. However, little is known about how intestinal GLP-1 affects distant organs despite rapid enzymatic inactivation. We show that intestinal GLP-1 inhibits gastric emptying and eating via intestinofugal neurons, a subclass of myenteric neurons that project to abdominal sympathetic ganglia. Remarkably, cell-specific ablation of intestinofugal neurons eliminated intestinal GLP-1 effects, and their chemical activation functioned as a GLP-1 mimetic. GLP-1 sensing by intestinofugal neurons then engaged a sympatho-gastro-spinal-reticular-hypothalamic pathway that links abnormal stomach distension to craniofacial programs for food rejection. Within this pathway, cell-specific activation of discrete neuronal populations caused systemic GLP-1-like effects. These molecularly identified, delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Activity in the dorsal vagal complex (DVC) is essential to gastric motility regulation. We and others have previously shown that this activity is greatly influenced by local GABAergic signaling, primarily because of somatostatin (SST)-expressing GABAergic neurons. To further understand the network dynamics associated with gastric motility control in the DVC, we focused on another neuron prominently distributed in this complex, neuropeptide-Y (NPY) neurons. However, the effect of these neurons on gastric motility remains unknown. Here, we investigate the anatomic and functional characteristics of the NPY neurons in the nucleus tractus solitarius (NTS) and their interactions with SST neurons using transgenic mice of both sexes. We sought to determine whether NPY neurons influence the activity of gastric-projecting neurons, synaptically interact with SST neurons, and affect end-organ function. Our results using combined neuroanatomy and optogenetic in vitro and in vivo show that NPY neurons are part of the gastric vagal circuit as they are trans-synaptically labeled by a viral tracer from the gastric antrum, are primarily excitatory as optogenetic activation of these neurons evoke EPSCs in gastric-antrum-projecting neurons, are functionally coupled to each other and reciprocally connected to SST neurons, whose stimulation has a potent inhibitory effect on the action potential firing of the NPY neurons, and affect gastric tone and motility as reflected by their robust optogenetic response in vivo. These findings indicate that interacting NPY and SST neurons are integral to the network that controls vagal transmission to the stomach. SIGNIFICANCE STATEMENT The brainstem neurons in the dorsal nuclear complex are essential for regulating vagus nerve activity that affects the stomach via tone and motility. Two distinct nonoverlapping populations of predominantly excitatory NPY neurons and predominantly inhibitory SST neurons form reciprocal connections with each other in the NTS and with premotor neurons in the dorsal motor nucleus of the vagus to control gastric mechanics. Light activation and inhibition of NTS NPY neurons increased and decreased gastric motility, respectively, whereas both activation and inhibition of NTS SST neurons enhanced gastric motility., (Copyright © 2022 the authors.)

Background: Gastroparesis can be a difficult problem with patients suffering from nausea, vomiting, bloating, and pain intractable to medical management. Gastric neurostimulation has been developed as an adjunctive treatment for patients with diabetic and idiopathic gastroparesis unresponsive to pharmacologic and dietary treatment. The purpose of this study is to report symptomatic and quality-of-life response to gastric neurostimulation.Methods: This study was approved by the institutional review board, and patients had informed consent. The gastric neurostimulation device (Enterra therapy, Medtronic, Inc., Minneapolis, MN, USA) is approved by the Food and Drug Administration under the Humanitarian Device Exemption. Candidates for placement were patients with either idiopathic or diabetic gastroparesis who had symptomatic failure to dietary changes and to prokinetic and antiemetic drugs. Before placement, the patients' symptoms were recorded, and patients completed the Gastrointestinal Symptom Rating Scale (GSRS, three domains: dyspeptic syndrome, indigestion syndrome, and bowel dysfunction syndrome) and the Short Form-36 (SF-36, eight domains: physical functioning, role-physical, role-emotional, bodily pain, vitality, mental health, social functioning, general health, plus a health transition item). The device was surgically placed using a hybrid laparoscopic/open technique. Patients were followed and adjustments made on the device until satisfactory symptom control was achieved. At that time, patients completed both the GSRS and SF-36, and comparisons were made to preoperative values.Results: Forty-two patients had the device placed, 29 women, aged 41 (SD +14) years, 24 diabetic patients, 17 idiopathic patients, one postgastrectomy patient. Median follow-up was 12 months (range 1-42 months). There was a 2% immediate postoperative morbidity rate and 7% long-term morbidity rate (device extrusion). Thirty-one patients (74%) responded to gastric neurostimulation of variable degrees. Eleven patients had no response or had worsening symptoms. Of the patients who responded, there were statistically significant improvements in all three domains of the GSRS. Median scores (with interquartile ranges): dyspeptic syndrome, 9 (7-11.5) to 4 (2.5-6), p = 0.02; indigestion syndrome, 5 (2-7) to 4 (0-5), p = 0.05; bowel dysfunction syndrome, 3 (2-3) to 1 (0-1), p = 0.01. In the SF-36, there were statistically significant improvement in the health transition item, 4 (4-5) to 1.5 (1-3), p = 0.01; and social functioning domain, 25 (12.5-62.5) to 75 (50-87.5), p = 0.03.Conclusions: Three quarters of gastroparesis patients responded to gastric neurostimulation to variable degrees. Gastrointestinal-specific symptoms are improved in responders. Patients felt that there health and social functioning (SF) improved, although there was no significant difference in the other domains. These results are encouraging considering that these patients had intractable symptoms with no other effective treatments available. [ABSTRACT FROM AUTHOR]

Abstract: Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition pre- or postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development. [Copyright &y& Elsevier]

Abstract: The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations or pharmacological manipulations. Therefore, a method using 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. [Copyright &y& Elsevier]

This study investigated the effect of gastric electrical stimulation (GES) on vagal activity and its possible vagal afferent-mediated mechanisms. Sixty rats implanted with gastric serosal electrodes were divided into six groups (control, vehicle, local capsaicin, perivagal capsaicin, systemic capsaicin, and vagotomy). GES with six sets of parameters was performed in the control group; and GES with one set of effective parameters was performed in the other five groups. Spectral analysis of heart rate variability was used to assess vagal activity. Regular gastric slow waves were recorded in the control rats with a frequency of 4.8 cycles/min. Vagotomy significantly reduced the frequency of the gastric slow wave but did not induce dysrhythmia. Capsaicin did not alter the gastric slow wave. Short-pulse (300-microsec) GES significantly increased vagal activity at a frequency four times the intrinsic slow-wave frequency. Stimulation at a lower frequency or with a long pulse (300 msec) had no effect on vagal activity. Vagotomy or capsaicin administered perivagally, systemically, or locally abolished the effect of GES on the vagal activity. GES with short but not long pulses is capable of altering vagal activity. This effect is mediated by capsaicin-sensitive vagal afferent fibers. [ABSTRACT FROM AUTHOR]

The influence of myenteric denervation on the development of gastric tumors induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) was studied after chemical denervation of the rat stomach with benzalkonium chloride (BAC). Three groups were evaluated: control, denervated and denervated with pyloroplasty. Random bred male Wistar rats were given MNNG in drinking water (100 mg/l) for 28 weeks. After the sacrifice of animals, the stomachs were removed for morphological study. BAC reduced myenteric neurons number, increased the gastric mucosa area and decreased the adenocarcinomas number and size. This decrease was more evident when denervation was associated with pyloroplasty. These results indicate that myenteric denervation reduces the incidence of experimentally induced gastric tumors. [Copyright &y& Elsevier]

Recent studies indicate that peripheral mechanisms contribute to the analgesic effect of amitriptyline. We hypothesized that amitriptyline inhibits voltage-dependent sodium currents in gastric sensory neurons. To label gastric neurons, the stomach was exposed in male Sprague Dawley rats through a midline incision to inject the retrograde tracer DiI into the gastric wall. Seven days after surgery, nodose ganglia were harvested. Neurons were dissociated and cultured for 4-24 hr to record whole cell sodium currents with the patch-clamp technique. Amitriptyline reversibly inhibited voltage-sensitive sodium currents with an IC50 of 20 microM. At clinically relevant concentrations, the peak sodium current decreased by about 15%. This was associated with a slowed recovery from inactivation, leading to a significantly enhanced cumulative inhibition during brief repetitive depolarizations. These findings are consistent with a use-dependent block of voltage-dependent sodium channels by amitriptyline. This effect may contribute to the analgesic properties of tricyclic antidepressants. [ABSTRACT FROM AUTHOR]

We investigated the possible involvement of the upper alimentary tract in vincristine (VCR)-induced dysmotility. Gastric contractions were recorded by a strain-gauge force transducer in conscious rats. Rats were injected with various doses of VCR followed by continuous recording for 12 hr. Additionally, 3-hr recordings to study the later effects were performed one and three days after injection. Gastric motility was dose-dependently increased by VCR. Post- versus preinjection motility index (MI; area under contraction waves) ratios were 0.78+/-0.12 for saline and 1.95+/-0.21 for VCR at 0.75 mg/kg. This increase in MI was completely inhibited by atropine and hexamethonium. MI one day after injection of VCR (0.75 mg/kg) was significantly less than in control (0.32+/-0.10 vs 0.92+/-0.24, respectively). The decrease was reversed by acetylcholine. In conclusion, VCR first increased gastric motility, and this was followed by a gradual decrease in conscious rats. These alterations may involve a presynaptic cholinergic pathway. [ABSTRACT FROM AUTHOR]

Some people attribute dyspeptic symptoms to drinking coffee, suggesting that coffee affects one or more functions of the proximal gastrointestinal tract. In a randomized controlled, cross-over, single-blinded study, the effects of coffee on gastric relaxation, gastric wall compliance and sensations, elicited by distension, were investigated in 10 healthy volunteers. Using the barostat technique, volume changes of an intragastric bag were recorded for 20 min after intragastric administration of 280 ml of coffee or water. Then, after deflation, the volume of the bag was increased stepwise every 3 min to assess gastric wall compliance and wall tension. At the end of every volume step, sensations (nausea, pain, and bloating) were scored. During the first 20 min after coffee administration, the volume change of the intragastric bag was larger than after water (P < 0.05). There were no differences in gastric wall compliance, wall tension, or symptom scores. In conclusions, coffee, in comparison with water, enhances the adaptive relaxation of the proximal stomach, but has no effect on its wall compliance, wall tension, or sensory function. [ABSTRACT FROM AUTHOR]

Examines the effects of vagal stimulation in the presence of muscarinic antagonist on three distinct rhythmically active cells in the antral region of guinea pig stomach. Inhibition of contractions of the circular muscle layer by vagal stimulation; Components of the inhibitory effect; Effect of vagal stimulation on electrical activity recorded from follower cells.

The purpose of this study was to examine if patients with functional dyspepsia could be separated into meaningful groups based on their autonomic function. Subjects were divided into two groups, and symptoms, gastric myoelectrical activity, gastric emptying, and psychological factors were compared. Group 1 had less autonomic variability but more cardiac reactivity than group 2. Symptom reports did not differ between groups. Group 1 had higher neuroticism scores than group 2, while group 2 showed greater tachyarrhythmia in response to drinking water than group 1. The relatively low autonomic variability in group 1 is consistent with higher sympathetic activity and may be associated with the group's greater neuroticism. The relative lack of cardiac reactivity in group 2 is consistent with lack of autonomic flexibility and may be related to the tachyarrhythmia observed in that group. The results of this study suggest that autonomic function may play a significant role in functional dyspepsia. [ABSTRACT FROM AUTHOR]

We investigated the distributions and targets of nitrergic neurons in the rat stomach, using neuronal nitric oxide synthase (NOS) immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. Nitrergic neurons comprised similar proportions of myenteric neurons, about 30%, in all gastric regions. Small numbers of nitrergic neurons occurred in submucosal ganglia. In total, there were ~ 125,000 neuronal nitric oxide synthase (nNOS) neurons in the stomach. The myenteric cell bodies had single axons, type I morphology and a wide range of sizes. Five targets were identified, the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the gastric wall. The circular and oblique muscle layers had nitrergic fibres throughout their thickness, while the longitudinal muscle was innervated at its inner surface by fibres of the tertiary plexus, a component of the myenteric plexus. There was a very dense innervation of the pyloric sphincter, adjacent to the duodenum. The muscle strands that run between mucosal glands rarely had closely associated nNOS nerve fibres. Both nNOS immunohistochemistry and NADPH histochemistry showed that nitrergic terminals did not provide baskets of terminals around myenteric neurons. Thus, the nitrergic neuron populations in the stomach supply the muscle layers and intramural arteries, but, unlike in the intestine, gastric interneurons do not express nNOS. The large numbers of nNOS neurons and the density of innervation of the circular muscle and pyloric sphincter suggest that there is a finely graded control of motor function in the stomach by the recruitment of different numbers of inhibitory motor neurons., (© 2022. The Author(s).)

Background/aim: Central administration of cocaine- and amphetamine-regulated transcript peptides (CARTp) alters gastrointestinal motility and reduces food intake in rats. Since neurons in the dorsal motor nucleus of the vagus (DMV) receive GABAergic and glutamatergic inputs and innervate the smooth muscle of gastrointestinal organs, we hypothesized that CARTp acts on the DMV or presynaptic neurons., Methods: We used 3,3'-dioctadecyloxa-carbocyanine perchlorate (DiO) retrograde tracing with electrophysiological methods to record DMV neurons innervating the stomach antrum or cecum in brainstem slices from adult rats., Results: DiO application did not change the electrophysiological properties of DMV neurons. CART55-102 had no effect on the basal firing rates of neurons in either the stomach antrum-labeled group (SLG) or cecum-labeled group (CLG). When presynaptic inputs were blocked, CART55-102 further increased the firing rates of the SLG, suggesting a direct excitatory effect. Spontaneous inhibitory postsynaptic currents (sIPSCs) occurred at a higher frequency in SLG neurons than in CLG neurons. CART55-102 reduced the amplitude and the frequency of sIPSCs in SLG neurons dose-dependently, with higher doses also reducing spontaneous excitatory postsynaptic currents (sEPSCs). Higher doses of CART55-102 reduced sIPSC and sEPSC amplitudes in CLG neurons, suggesting a postsynaptic effect. In response to incremental current injections, the SLG neurons exhibited less increases in firing activity. Simultaneous applications of current injections and CART55-102 decreased the firing activity of the CLG. Therefore, stomach antrum-projecting DMV neurons possess a higher gating ability to stabilize firing activity., Conclusion: The mechanism by which CARTp mediates anorectic actions may be through a direct reduction in cecum-projecting DMV neuron excitability and, to a lesser extent, that of antrum-projecting DMV neurons, by acting on receptors of these neurons., (© 2021 S. Karger AG, Basel.)

We previously reported P2X3 purinoceptor (P2X3)-expressing vagal afferent nerve endings with large web-like structures in the subserosal tissue of the antral lesser curvature, suggesting that these nerve endings were one of the vagal mechanoreceptors. The present study investigated the morphological relationship between P2X3-immunoreactive nerve endings and serosal ganglia in the rat gastric antrum by immunohistochemistry of whole-mount preparations using confocal scanning laser microscopy. P2X3-immunoreactive basket-like subserosal nerve endings with new morphology were distributed laterally to the gastric sling muscles in the distal antrum of the lesser curvature. Parent axons ramified into numerous nerve fibers with pleomorphic flattened structures to form basket-like nerve endings, and the parent axons were originated from large net-like structures of vagal afferent nerve endings. Basket-like nerve endings wrapped around the whole serosal ganglia, which were characterized by neurofilament 200 kDa-immunoreactive neurons with or without neuronal nitric oxide synthase immunoreactivity and S100B-immunoreactive glial cells. Furthermore, basket-like nerve endings were localized in close apposition to dopamine beta-hydroxylase-immunoreactive sympathetic nerve fibers immunoreactive for vesicular nucleotide transporter. These results suggest that P2X3-immunoreactive basket-like nerve endings associated with serosal ganglia are the specialized ending structures of vagal subserosal mechanoreceptors in order to increase the sensitivity during antral peristalsis, and are activated by ATP from sympathetic nerve fibers and/or serosal ganglia for the regulation of mechanoreceptor function., (© 2021 Wiley Periodicals LLC.)

Reparative perineural hyperplasia is an incidental and probably underreported reactive histologic finding thus far only reported in the setting of healing wounds or adjacent to a dermatofibroma in cutaneous specimens. It is characterized by a focal concentric proliferation of cytologically bland spindled perineurial cells and is hence considered a benign histologic mimic of neoplastic perineural invasion. Thus, it may present a diagnostic pitfall and we therefore consider it as a valuable entity to be aware of. To the best of our knowledge, this brief case report is the first to convey that reparative perineural hyperplasia may also occur in the gastrointestinal tract. It may therefore be a ubiquitous reactive histological phenomenon relating to previous surgical or traumatic wounds in various sites, that is, outside the thus far established setting of skin reexcision specimens.

Records in vitro gastric vagal afferents' (GVA) unit activities from ventral GVA nerve strands in rats. Comparison of the responsiveness of GVA terminals to intraarterial injection of leptin and cholecystokinin; Identification of two types of leptin-responsive GVA terminals.

Investigates electrophysiologically the effect of systemic cholecystokinin (CCK) on the discharge of vagal gastric mechanoreceptors. Responses to CCK octapeptide; Gastric distention; Vagal afferent fibers; Firing time.

Investigates the role of capsaicin-sensitive afferent innervation and neural pathways involved in the enterogastric inhibition of gastric acid secretion by luminal acid. Central nervous system; Brain-gut axis; Extrinsic reflexes; Sensory afferents; Thyrotropin-releasing hormone analogue; Pentagastrin.

Examines the feasibility of an antral reinnervation by microsurgical vagorrhapy and vagoplasty. Potential for regeneration of the abdominal vagal nerves in rats; Recovery of gastric secretory and motor functions; Vagal regeneration and innervation; Postvagotomy gastroparesis.

Investigates the effects of nitric oxide (NO) synthesis inhibitors on nonadrenergic, noncholinergic relaxations elicited by electrical field stimulation in the gastric circular muscle of the rabbit. Reduction in sustained relaxant responses; Indication that the inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway.

Investigates the gastrogastric reflexes that regulate gastric tone in humans and their relationship to perception. Measurement of responses to gastric filling and thermal stimulation; Indication that gastric tone is modulated by a net of reflexes that arise from the proper wall of the stomach below the discomfort zone.

Surface electrogastrography was performed in 18 patients with esophageal atresia (EA) and 10 normal controls to investigate the possible role of a congenital enteric nerve defect as a cause of gastroesophageal reflux (GER), which is common after repair of EA. The means of the dominant frequencies and ranges of the frequency distribution were compared. The dominant frequencies (0.047+/-0.007 Hz) in the EA group did not differ significantly from those of the controls (0.050+/-0.007 Hz, P >0.1), although 2 patients had bradygastria and 2 had tachygastria in the EA group. The range of the frequency distribution was significantly wider in the EA group compared with normal children (P = 0.002). The wide frequency distribution in children with EA suggests disturbed electrical activity of the stomach, which could be associated with poor electromechanical coupling and, hence abnormal gastric contraction. [ABSTRACT FROM AUTHOR]

The effect of chemical deafferentation, vagotomy (VGX), and gangliosympathectomy (GSX) on the density of fibers containing calcitonin gene-related peptide (CGRP) and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation by capsaicin abolished the density of CGRP-immunoreactive (IR) fibers, not Sub.P-IR fibers. Ten days after VGX, the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reduction of CGRP-IR and Sub.P-IR fibers was seen in submucosal and muscular layers. GSX significantly reduced the density of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosal and muscular layers. Pretreatment with 6-hydroxydopamine, a neurotoxin for noradrenergic nerves, did not affect the density of CGRP-IR fibers in the gastric wall. The density of Sub.P-IR fibers in the gastric wall was not affected by GSX. These studies indicate that the CGRP-IR and Sub.P-IR fibers in the mucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and muscle layers, that a major portion of the CGRP-IR fibers in the mucosa is of both vagal and spinal origin, and that a major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, the present results support that CGRP-IR fibers, not Sub.P-IR fibers, in the rat stomach are capsaicin-sensitive. [ABSTRACT FROM AUTHOR]

Presents a study regarding the effect of resection of the sympathetic and parasympathetic innervation of the stomach upon gastric acidity. Medical tests used before and after surgery; Variable that offers an assurance that acidiy is below the critical level; Factors which influence the secretion of hydrochloric acid.

Discusses the conservative surgical treatment of complicated duodenal ulcer. Acceptable operations for the treatment of complicated duodenal ulcer; Historical findings on gastroduodenostomy; Rationale for the employment of gastroduodenostomy with a small stoma placed near the pylorus and with preservation of vagal innervation.

Background: The motor protein, Myosin 5a (Myo5a) is known to play a role in inhibitory neurotransmission in gastric fundus. However, there is no information regarding the relative expression of total Myo5a, or of its alternative exon splice variants, across the stomach. This study investigated the differential distribution of Myo5a variants expressed within distinct anatomical regions of murine stomach., Methods: The distribution of Myo5a protein and mRNA in the stomach was assessed by immunofluorescence microscopy and fluorescent in situ hybridization. Quantitative PCR, restriction enzyme analysis, and electrophoresis were used to identify Myo5a splice variants and quantify their expression levels in the fundus, body, antrum, and pylorus., Key Results: Myo5a protein colocalized with βIII-Tubulin in the myenteric plexus, and with synaptophysin in nerve fibers. Total Myo5a mRNA expression was lower in pylorus than in antrum, body, or fundus (p < 0.001), which expressed equivalent amounts of Myo5a. However, Myo5a splice variants were differentially expressed across the stomach. While the ABCE splice variant predominated in the antrum and body regions, the ACEF/ACDEF variants were enriched in fundus and pylorus., Conclusions and Inferences: Myo5a splice variants varied in their relative expression across anatomically distinguishable stomach regions and might mediate distinct physiological functions in gastric neurotransmission., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Simple Summary: Bisphenol A (BPA) is a well-known endocrine disruptor, widely distributed in the environment because of its use in the plastic production process all over the world. After getting into a living organism, due to its similarity to estrogen, it affects many organs and systems, including the nervous and gastrointestinal systems. The enteric nervous system (ENS) in the wall of the gastrointestinal tract is responsible for regulation of the function of stomach and intestine. The ENS, due to a vast number of nerve cells and a high independence from the central nervous system, is often called the "intestinal" or "second" brain. It should be highlighted that the influence of BPA on the ENS has not been fully investigated so far. Therefore, the present study focuses on the effect of BPA on the ENS of the porcine stomach. It should also be highlighted that the domestic pig is a great animal model for investigations of the influence of pathological factors on the human ENS. Therefore the results of this research will help to understand the effect of BPA on the ENS of the human stomach. Bisphenol A (BPA) is widely utilized in plastic production process all over the world. Previous studies have shown that BPA, with its similarity to estrogen, may negatively affect living organisms. It is acknowledged that BPA distorts the activity of multiple internal systems, including the nervous, reproductive, urinary, and endocrine systems. BPA also affects the gastrointestinal tract and enteric nervous system (ENS), which is placed throughout the wall from the esophagus to the rectum. Contrary to the intestine, the influence of BPA on the ENS in the stomach is still little known. This study, performed using the double immunofluorescence method, has revealed that BPA affects the number of nervous structures in the porcine gastric wall immunoreactive to vesicular acetylcholine transporter (VAChT, a marker of cholinergic neurons), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL) and cocaine- and amphetamine-regulated transcript peptide (CART). The character and severity of noted alterations depended on the part of the ENS, the BPA dose, and the type of neuronal substance. Administration of BPA resulted in an increase in the number of nervous structures containing SP, GAL, and/or CART, and a decrease in the number of cholinergic neurons in all parts of the gastric wall. The number of VIP-positive nervous structures increased in the enteric myenteric ganglia, along with the muscular and mucosal layers, whilst it decreased in the submucous ganglia. The exact mechanism of noted changes was not absolutely obvious, but they were probably related to the neuroprotective and adaptive processes constituting the response to the impact of BPA. [ABSTRACT FROM AUTHOR]

Purpose: Vagus nerve injuries during gastroesophageal surgery may cause significant symptoms due to loss of vagal anti-inflammatory and neuromodulator function. Many previous studies have shown high anatomical variability of the vagus nerve at the esophageal hiatus, but information on its variability in Uganda specifically and Africa in general is scanty. This study provides a reliable and detailed description of the anatomical variation and distribution of the vagus nerve in the esophageal hiatus region of post-mortem cases in Uganda., Methods: This was an analytical cross-sectional survey of 67 unclaimed post-mortem cases. Data collection used a pretested data collection form. Data were entered into Epi-Info version 6.0 data base then exported into STATA software 13.0 for analysis., Results: The pattern of the anterior vagal trunk structures at the esophageal hiatus was: single trunk [65.7%]; biplexus [20.9%]; triplexus [8.9%] and double-but-not-connected trunks [4.5%]. The pattern of the posterior trunk structures were: single trunk [85.1%]; biplexus 10.4% and triplexus [4.5%]. There was no statistically significant gender difference in the pattern of vagal fibres. There was no major differences in the pattern from comparable British studies., Conclusion: The study confirmed high variability in the distribution of the vagus nerve at the esophageal hiatus, unrelated to gender differences. Surgeons must consider and identify variants of vagal innervation when carrying out surgery at the gastroesophageal junction to avoid accidental vagal injuries. Published surgical techniques for preserving vagal function are valid in Uganda., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

The vagus nerve innervates many organs, and most, if not all, of its motor fibers are cholinergic. However, no one knows its organizing principles-whether or not there are dedicated neurons with restricted targets that act as "labeled lines" to perform certain functions, including two opposing ones (gastric contraction versus relaxation). By performing unbiased transcriptional profiling of DMV cholinergic neurons, we discovered seven molecularly distinct subtypes of motor neurons. Then, by using subtype-specific Cre driver mice, we show that two of these subtypes exclusively innervate the glandular domain of the stomach where, remarkably, they contact different enteric neurons releasing functionally opposing neurotransmitters (acetylcholine versus nitric oxide). Thus, the vagus motor nerve communicates via genetically defined labeled lines to control functionally unique enteric neurons within discrete subregions of the gastrointestinal tract. This discovery reveals that the parasympathetic nervous system utilizes a striking division of labor to control autonomic function., Competing Interests: Declaration of interests S.D.L. is a consultant for Kallyope, Inc., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nutrient sensors allow animals to identify foods rich in specific nutrients. The Drosophila nutrient sensor, diuretic hormone 44 (DH44) neurons, helps the fly to detect nutritive sugar. This sensor becomes operational during starvation; however, the mechanisms by which DH44 neurons or other nutrient sensors are regulated remain unclear. Here, we identified two satiety signals that inhibit DH44 neurons: (1) Piezo-mediated stomach/crop stretch after food ingestion and (2) Neuromedin/Hugin neurosecretory neurons in the ventral nerve cord (VNC) activated by an increase in the internal glucose level. A subset of Piezo + neurons that express DH44 neuropeptide project to the crop. We found that DH44 neuronal activity and food intake were stimulated following a knockdown of piezo in DH44 neurons or silencing of Hugin neurons in the VNC, even in fed flies. Together, we propose that these two qualitatively distinct peripheral signals work in concert to regulate the DH44 nutrient sensor during the fed state., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)