Neurons Of Enteric Nervous System Research Articles

Alteration in the neurochemical profile of ENS neurons in the porcine ileum after oral exposure of glyphosate

Glyphosate-based herbicides are one of the most intensively used pollutants worldwide. The main goal of present study was to determine the changes in the neurochemical phenotype of enteric nervous system (ENS) neurons in the porcine ileum after oral glyphosate administration.Study was performed on 15 immature gilts divided into 3 groups: control (C) - animals receiving empty gelatin capsules; G1 - animals receiving a low dose of glyphosate- corresponding to the theoretical maximum daily intake (TMDI) - 0.05 mg/kg of b.w./day; G2- animals receiving a higher dose of glyphosate - corresponding to the acceptable daily intake (ADI) - 0.5 mg/kg of b.w./day) in gelatin capsules orally for 28 days. After this time, the animals were euthanized and ileum samples were collected. Frozen sections (12μm thick) were then subjected to the double immunofluorescent staining technique using primary antibody directed towards Hu C/D (used as a pan-neuronal marker) and pituitary adenylate cyclase-activating polypeptide (PACAP), neuronal nitric oxide synthase (nNOS), vesicular acetylcholine transporter (VAChT), cocaine and amphetamine-regulated transcript (CART) and appropriate secondary antibodies.Supplementation of lower dose of glyphosate increased the population of PACAP- like immunoreactive (LI) neurons in the outer submucous plexus (OSP) (from 6.34±1.24 to 14.12±1.68%), nNOS-LI neurons in the myenteric plexus (MP) (from 29.96±2.40 to 37.57±1.17%) and the inner submucous plexus (ISP) (from 12.64±1.10 to 19.76±1.34%), CART-LI neurons in the MP (from 20.44±0.81 to 29.77±1.16%) and the ISP (from 6.07±1.00 to 10.44±0.94%) and decreased the number of VAChT-LI neurons in both submucous plexuses (from 30.69±1.22 to 24.84±1.20% in the OSP and from 53.03±1.67 to 46.68±1.18% in the ISP). The higher dose of glyphosate evoke marked changes in the immunoreactivity of all neuroactive substance studied and type of enteric plexus analyzed. An increased number of PACAP-LI (from 13.75±to 40.20 to 40.20±1.62% in the MP, to 21.12 ±1.40% in the OSP and from 11.22±1.26 to 34.94±1.61% in the ISP), nNOS-LI (to 49.92±1.73% in the MP, from 19.53±1.29 to 27.69±1.29% in the OSP and to 27.92±1.26% in the ISP), CART-LI (to 35.03±1.67% in the MP, from 10.60±1.38 to 22.23±1.27% in the OSP and to14.78±1.53% in the ISP) neurons as well as a decrease in the population of VAChT-LI neurons (from 44.58±1.82 to 29.03±1.74% in the MP, to 22.24±1.96% in the OSP and to 35.87±1.42% in the ISP) were noted.Observed changes may result from neurotoxic effect of glyphosate on the ENS neurons and be part of adaptive processes of these neurons to ileum dysfunction. the National Science Centre in Poland [grant no. 2020/04/X/NZ7/00338]. Project financially supported by the Minister of Education and Science under the program entitled “Regional Initiative of Excellence” for the years 2019-2023, Project No. 010/RID/2018/19, amount of funding 12.000.000 PLN. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Progesterone: A Neuroprotective Steroid of the Intestine.

The enteric nervous system (ENS) is an intrinsic network of neuronal ganglia in the intestinal tube with about 100 million neurons located in the myenteric plexus and submucosal plexus. These neurons being affected in neurodegenerative diseases, such as Parkinson's disease, before pathological changes in the central nervous system (CNS) become detectable is currently a subject of discussion. Understanding how to protect these neurons is, therefore, particularly important. Since it has already been shown that the neurosteroid progesterone mediates neuroprotective effects in the CNS and PNS, it is now equally important to see whether progesterone has similar effects in the ENS. For this purpose, the RT-qPCR analyses of laser microdissected ENS neurons were performed, showing for the first time the expression of the different progesterone receptors (PR-A/B; mPRa, mPRb, PGRMC1) in rats at different developmental stages. This was also confirmed in ENS ganglia using immunofluorescence techniques and confocal laser scanning microscopy. To analyze the potential neuroprotective effects of progesterone in the ENS, we stressed dissociated ENS cells with rotenone to induce damage typical of Parkinson's disease. The potential neuroprotective effects of progesterone were then analyzed in this system. Treatment of cultured ENS neurons with progesterone reduced cell death by 45%, underscoring the tremendous neuroprotective potential of progesterone in the ENS. The additional administration of the PGRMC1 antagonist AG205 abolished the observed effect, indicating the crucial role of PGRMC1 with regard to the neuroprotective effect of progesterone.

P071 T-cell, B-cell and monocytic infiltrations of myenteric plexus in IBD

Abstract Background Patients suffering from IBD frequently suffer from chronic visceral pain, severely affecting quality of life. To better understand factors impacting pain signaling by enteric nervous system (ENS) neuronal cells, we analyzed the infiltration of the myenteric plexus (MP) of the ENS by inflammatory cell populations. In detail, we characterized (i) the immune cell populations infiltrating the MP, (ii) neurotransmitter expression by MP cells and (iii) neuronal cell survival of MP in Crohn’s disease (CD) and ulcerative colitis (UC). Methods We included 12 UC and nine CD patients that received colectomies or ileocecal resections, respectively, and 10 control patients with surgeries for non-inflammatory reasons. FFPE material was used for immunohistochemistry analysis of the MP. Immunostaining was performed for the detection of ENS neurons (beta-III tubulin, PGP9.5), for T-cells (CD3, CD4, CD8 and FOXP3), for B-cells (CD20), for monocytes (CD68, CD163) and apoptosis (Annexin V) and the neurotransmitters CGRP and substance P. Intraganglionic and periganglionic immune cell populations were determined by conventional LSM confocal microscopy. Results CD3+ and CD8+ intraganglionic T-cells for CD (CD3+: 1.7 ± 0.6 cells/10.000 µm²; CD8+: 4.8 ± 1.1 cells/10.000 µm²) were found to be increased compared to control patients (CD3+: 0.2 ± 0.1 cells/10.000 µm², p=0.04; CD8+: 0.4 ± 0.2 cells/10.000 µm², p=0.006), Figure 1. CD20+ B-cells and CD68+ monocytes were significantly increased in CD MP as well (CD20+ B-cells in CD: 0.8 cells/10.000 µm², CD20+ B-cells in controls: 0 cells/10.000 µm, p=0.02), CD68+ monocytes in CD: 12.3 cells/10.000 µm², CD68+ monocytes in controls: 3.5 cells/10.000 µm², p=0.001). CD8+ cytotoxic T-cells infiltrating the periganglionic area of the MP were significantly increased for UC. 1.6-fold increased expression of the neurotransmitter CGRP were detected for UC MP, p=0.01. Substance P was found to be 0.7-fold reduced for CD MP, p=0.01. MP-cell survival (Annexin V) was found to be reduced for UC MP, p=0.048. Figure 2 shows representative neurotransmitter immunostainings in two patients per condition. Conclusion In conclusion, MP immune cell infiltrations in CD are comprised of CD3+, CD8+ T-cells as well as CD68+ monocytes and CD20+ B-cells. Specifically periganglionically, CD8+ T-cells are found in UC. The expression of the neurotransmitter CGRP is increased in CD-MPs whereas levels of substance P are reduced in UC MP. UC-affected MPs revealed higher levels of apoptosis.

Isolation and transfection of myenteric neurons from mice for patch-clamp applications.

The enteric nervous system (ENS) is a complex neuronal network organized in ganglionated plexuses that extend along the entire length of the gastrointestinal tract. Largely independent of the central nervous system, the ENS coordinates motility and peristalsis of the digestive tract, regulates secretion and absorption, and is involved in immunological processes. Electrophysiological methods such as the patch-clamp technique are particularly suitable to study the function of neurons as well as the biophysical parameters of the underlying ion channels under both physiological and pathophysiological conditions. However, application of the patch-clamp method to ENS neurons remained difficult because they are embedded in substantial tissue layers that limit access to and targeted manipulation of these cells. Here, we present a robust step-by-step protocol that involves isolation of ENS neurons from adult mice, culturing of the cells, their transfection with plasmid DNA, and subsequent electrophysiological characterization of individual neurons in current-clamp and voltage-clamp recordings. With this protocol, ENS neurons can be prepared, transfected, and electrophysiologically characterized within 72 h. Using isolated ENS neurons, we demonstrate the feasibility of the approach by functional overexpression of recombinant voltage-gated NaV1.9 mutant channels associated with hereditary sensory and autonomic neuropathy type 7 (HSAN-7), a disorder characterized by congenital analgesia and severe constipation that can require parenteral nutrition. Although our focus is on the electrophysiological evaluation of isolated ENS neurons, the presented methodology is also useful to analyze molecules other than sodium channels or to apply alternative downstream assays including calcium imaging, proteomic and nucleic acid approaches, or immunochemistry.

Immunodetection of P2X2 Receptor in Enteric Nervous System Neurons of the Small Intestine of Pigs.

Extracellular adenosine 5'-triphosphate (ATP) is one of the best-known and frequently studied neurotransmitters. Its broad spectrum of biological activity is conditioned by the activation of purinergic receptors, including the P2X2 receptor. The P2X2 receptor is present in the central and peripheral nervous system of many species, including laboratory animals, domestic animals, and primates. However, the distribution of the P2X2 receptor in the nervous system of the domestic pig, a species increasingly used as an experimental model, is as yet unknown. Therefore, this study aimed to determine the presence of the P2X2 receptor in the neurons of the enteric nervous system (ENS) of the pig small intestine (duodenum, jejunum, and ileum) by the immunofluorescence method. In addition, the chemical code of P2X2-immunoreactive (IR) ENS neurons of the porcine small intestine was analysed by determining the coexistence of selected neuropeptides, i.e., vasoactive intestinal polypeptide (VIP), substance P (sP), and galanin. P2X2-IR neurons were present in the myenteric plexus (MP), outer submucosal plexus (OSP), and inner submucosal plexus (ISP) of all sections of the small intestine (duodenum, jejunum, and ileum). From 44.78 ± 2.24% (duodenum) to 63.74 ± 2.67% (ileum) of MP neurons were P2X2-IR. The corresponding ranges in the OSP ranged from 44.84 ± 1.43% (in the duodenum) to 53.53 ± 1.21% (in the jejunum), and in the ISP, from 53.10 ± 0.97% (duodenum) to 60.57 ± 2.24% (ileum). Immunofluorescence staining revealed the presence of P2X2-IR/galanin-IR and P2X2-IR/VIP-IR neurons in the MP, OSP, and ISP of the sections of the small intestine. The presence of sP was not detected in the P2X2-IR neurons of any ganglia tested in the ENS. Our results indicate for the first time that the P2X2 receptor is present in the MP, ISP, and OSP neurons of all small intestinal segments in pigs, which may suggest that its activation influences the action of the small intestine. Moreover, there is a likely functional interaction between P2X2 receptors and galanin or VIP, but not sP, in the ENS of the porcine small intestine.

Glyphosate affects the neurochemical phenotype of the intramural neurons in the duodenum in the pig.

Glyphosate-based herbicides have been one of the most intensively used pollutants worldwide and food products containing glyphosate are an essential component of human and animal diet. The aim of present study was to determine the effect of glyphosate intoxication on the neurochemical properties of the enteric nervous system (ENS) neurons located in the wall of the porcine duodenum. Fifteen sexually immature gilts divided into 3 groups were used: control-animals receiving empty gelatin capsules; G1-animals receiving a low dose of glyphosate-corresponding to the theoretical maximum daily intake (TMDI) - 0.05 mg/kg bw/day; G2-animals receiving a higher dose of glyphosate-corresponding to the acceptable daily intake (ADI)-0.5mg/kg/day in gelatin capsules orally for 28 days. After this time, the animals were euthanized and small intestine samples were collected. Frozen sections were then subjected to the procedure of double immunofluorescent staining. Glyphosate supplementation led to alterations in the neurochemical code of the ENS neurons in the porcine duodenum. Generally, increased population of neurons immunoreactive to PACAP, CGRP, CART, nNOS, and a decreased number of VAChT-like immunoreactive neurons were noted. It may be a first preclinical symptom of digestive tract dysfunction in the course of glyphosate intoxication and further studies are needed to assess the toxicity and risks of glyphosate to humans.

A New Transgenic Tool to Study the Ret Signaling Pathway in the Enteric Nervous System

The receptor tyrosine kinase Ret plays a critical role in regulating enteric nervous system (ENS) development. Ret is important for proliferation, migration, and survival of enteric progenitor cells (EPCs). Ret also promotes neuronal fate, but its role during neuronal differentiation and in the adult ENS is less well understood. Inactivating RET mutations are associated with ENS diseases, e.g., Hirschsprung Disease, in which distal bowel lacks ENS cells. Zebrafish is an established model system for studying ENS development and modeling human ENS diseases. One advantage of the zebrafish model system is that their embryos are transparent, allowing visualization of developmental phenotypes in live animals. However, we lack tools to monitor Ret expression in live zebrafish. Here, we developed a new BAC transgenic line that expresses GFP under the ret promoter. We find that EPCs and the majority of ENS neurons express ret:GFP during ENS development. In the adult ENS, GFP+ neurons are equally present in females and males. In homozygous mutants of ret and sox10-another important ENS developmental regulator gene-GFP+ ENS cells are absent. In summary, we characterize a ret:GFP transgenic line as a new tool to visualize and study the Ret signaling pathway from early development through adulthood.

Administration of Different Doses of Acrylamide Changed the Chemical Coding of Enteric Neurons in the Jejunum in Gilts.

Excessive consumption of highly processed foods, such as chips, crisps, biscuits and coffee, exposes the human to different doses of acrylamide. This chemical compound has a multidirectional, adverse effect on human and animal health, including the central and peripheral nervous systems. In this study, we examined the effect of different doses of acrylamide on the enteric nervous system (ENS) of the porcine jejunum. Namely, we took into account the quantitative changes of neurons located in the jejunum wall expressing substance P (SP), galanin (GAL), a neuronal form of nitric oxide synthase (nNOS), the vesicular acetylcholine transporter (VAChT) and cocaine- and amphetamine-regulated transcript (CART). The obtained results indicate that acrylamide causes a statistically significant increase in the number of neurons immunoreactive to SP, GAL, VAChT and CART in all types of examined enteric plexuses and a significant drop in the population of nNOS-positive enteric neurons. Changes were significantly greater in the case of a high dose of acrylamide intoxication. Our results indicate that acrylamide is not indifferent to ENS neurons. A 28-day intoxication with this substance caused marked changes in the chemical coding of ENS neurons in the porcine jejunum.

Adult Neurogenesis in the Gut, Homeostatic Autoimmunity and Neurodegenerative Disease Biomarkers

Autoantibodies to neuronal antigens are viewed as potential biomarkers for neurodegenerative diseases. Increasing evidence, however, suggests a dissociation of the neurodegenerative process in the central nervous system and dynamics of neuronal proteins in peripheral circulation with the prevalence of a wide variety of immunoglobulins reactive to neuronal antigens reported also in the blood of healthy subjects, including children. Recently discovered physiological turnover of neurons in enteric nervous system with release of neuronal proteins in peripheral circulation may account for this conundrum and provide a new perspective on molecular biomarkers of neurodegenerative diseases and immunotherapy.

Gut Bacteria and Neurotransmitters.

Gut bacteria play an important role in the digestion of food, immune activation, and regulation of entero-endocrine signaling pathways, but also communicate with the central nervous system (CNS) through the production of specific metabolic compounds, e.g., bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) and histamine. Afferent vagus nerve (VN) fibers that transport signals from the gastro-intestinal tract (GIT) and gut microbiota to the brain are also linked to receptors in the esophagus, liver, and pancreas. In response to these stimuli, the brain sends signals back to entero-epithelial cells via efferent VN fibers. Fibers of the VN are not in direct contact with the gut wall or intestinal microbiota. Instead, signals reach the gut microbiota via 100 to 500 million neurons from the enteric nervous system (ENS) in the submucosa and myenteric plexus of the gut wall. The modulation, development, and renewal of ENS neurons are controlled by gut microbiota, especially those with the ability to produce and metabolize hormones. Signals generated by the hypothalamus reach the pituitary and adrenal glands and communicate with entero-epithelial cells via the hypothalamic pituitary adrenal axis (HPA). SCFAs produced by gut bacteria adhere to free fatty acid receptors (FFARs) on the surface of intestinal epithelial cells (IECs) and interact with neurons or enter the circulatory system. Gut bacteria alter the synthesis and degradation of neurotransmitters. This review focuses on the effect that gut bacteria have on the production of neurotransmitters and vice versa.

Efficacy of Qihuang decoction on enteric nervous system in rats after gastrectomy.

To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats. The morphology, distribution and number of intestinal neurons in enteric nervous system (ENS) were observed by immunofluorescence labeling and confocal laser scanning microscopy. Reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of intestinal neurotransmitters and corresponding receptors in ENS. The morphology and distribution of enteric neurons in ENS were changed after gastrectomy, and these neurons in Qihuang decoction group were similar with that of sham operation group. The number of ACh and SP positive neurons, mRNA and protein expression of excitatory neurotransmitters (AChE, SP) and receptors (M3R, NK1R) were decreased after gastrectomy. And the intervention of Qihuang decoction could increase the number of ACh and SP positive neurons and promote the expression of their mRNA and protein. For vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), the number of neurons and mRNA and protein expression of inhibitory neurotransmitters (VIP and NOS) and receptors (VIP2R) were increased after gastrectomy. And these rising indexes fall back after the intervention of Qihuang decoction. Besides, the intestinal propulsion rate in QH group was significantly increased than that in SEN and IEN group. These experimental results showed that after gastrectomy, early intervention with Qihuang decoction in small intestine will contribute to the postoperative recovery of enteric nervous system and intestinal propulsion rate, and consequently enhance gastrointestinal motility.

Characterization of Neurochemical Signature Alterations in the Enteric Nervous System in Autoimmune Encephalomyelitis

To date, it has remained unclear whether gastrointestinal symptoms, which are frequently observed in patients with multiple sclerosis (MS), are accompanied by pathology of the enteric nervous system (ENS). Here, the neurotransmitter signature of ENS neurons and morphological alterations of interstitial cells of Cajal (ICCs) were studied in patients with MS and mice with experimental autoimmune encephalomyelitis (EAE), which is an animal model of MS. Immunohistochemical analysis was performed on colonic whole mounts from mice with EAE and on paraffin-embedded sections of intestinal tissue from patients with MS. Antibodies against neurotransmitters or their enzymes (including vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT)) were used in conjunction with pan-neuronal markers. In addition, the presence of anoctamin 1 (ANO1)-expressing ICCs was studied. ENS changes were observed in the myenteric plexus, but they were absent in the submucosal plexus of both EAE mice and patients with MS. There was a significant decrease in the percentage of ChAT-positive neurons in EAE mice as opposed to a trend toward an increase in patients with MS. Moreover, while ANO1 expression was decreased in EAE mice, patients with MS displayed a significant increase. Although additional studies are necessary to accomplish an in-depth characterization of ENS alterations in MS, our results imply that such alterations exist and may reveal novel insights into the pathophysiology of MS.

Pyrroloquinoline Quinone Regulates Enteric Neurochemical Plasticity of Weaned Rats Challenged With Lipopolysaccharide.

The enteric nervous system (ENS) is important for the intestinal barrier to defend and regulate inflammation in the intestine. The aim of this study was to investigate the effect of pyrroloquinoline quinone (PQQ) on regulating neuropeptide secretion by ENS neurons of rats challenged with lipopolysaccharide (LPS) to create enteritis. Thirty Sprague Dawley rats were divided into five groups, namely, basal (CTRL), basal plus LPS challenge (LPS), basal with 2.5 mg/kg b.w./day of PQQ plus challenge with LPS (PQQ 2.5), basal with 5.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 5), and basal with 10.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 10). After treatment with basal diet or PQQ for 14 days, rats were challenged with LPS except for the CTRL group. Rats were euthanized 6 h after the LPS challenge. Rats showed an increased average daily gain in PQQ treatment groups (P < 0.05). Compared with the LPS group, PQQ 5 and PQQ 10 rats showed increased villus height and villus height/crypt depth of jejunum (P < 0.05). In PQQ treatment groups, concentrations of IL-1β and TNF-α in serum and intestine of rats were decreased, and IL-10 concentration was increased in serum compared with the LPS group (P < 0.05). Compared with the LPS group, the concentration of neuropeptide Y (NPY), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and brain-derived neurotropic factor (BDNF) in serum were decreased in PQQ treatment groups (P < 0.05). Compared with the LPS group, ileal mRNA levels of BDNF, NPY, and NGF were decreased in PQQ treatment groups (P < 0.05). Jejunal concentrations of SP, CGRP, VIP, BDNF, NPY, and NGF were decreased in PQQ treatment groups compared with the LPS group (P < 0.05). Compared with the LPS group, phosphor-protein kinase B (p-Akt)/Akt levels in jejunum and colon were decreased in PQQ treatment groups (P < 0.05). In conclusion, daily treatment with PQQ improved daily gain, jejunal morphology, immune responses. PQQ-regulated enteric neurochemical plasticity of ENS via the Akt signaling pathway of weaned rats suffering from enteritis.

Stress‐Induced Gut Dysmotility is Associated with Altered Intestinal BDNF‐TrkB Signaling

IntroductionWhile stress is associated with incidence of gut dysmotility disorders, mechanisms by which stress causes dysmotility are not well understood. In the central nervous system (CNS), stress causes behavioral deficits by increasing the levels of Glucocorticoid hormone to suppress molecular signaling between brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). We hypothesize that stress causes a Glucocorticoid‐mediated reduction in BDNF‐TrkB signaling in the enteric nervous system (ENS), whose neurons, which modulate diverse gut functions, reside entirely within the gut wall.MethodsGut motility was assayed by analyzing the whole gut transit time (WGTT) of an orally gavaged carmine red dye in adult mice. Effect of stress was tested by comparing WGTT of Stress‐Induced Dysmotility (SID) mice, wherein age‐matched adult male mice were restrained for one hour, with that of unrestrained control mice. The effect of Glucocorticoids was tested by comparing WGTT of age‐matched adult C57/BL6 male mice dosed with Dexamethasone (DEX, a Glucocorticoid receptor agonist, intra‐peritoneal 5mg/kg), with that of saline‐dosed control mice. Effect of DEX on enteric BDNF levels (using R&amp;D ELISA kit) was tested by using total proteins isolated from preparations of adult murine longitudinal muscle‐myenteric plexus (LM‐MP) tissues cultured with and without DEX (1 µM) for 4 hours. TrkB exists in full‐length and truncated (TrkB.T1) isoforms, and the presence of TrkB.T1 in ENS neurons was observed by immunofluorescence analyses of ENS tissue of TrkB.T1‐V5 transgenic mice. Involvement of TrkB.T1 isoform in SID was tested by comparing WGTT of male transgenic mice containing partial (T1‐Het) or complete loss (T1 KO) of TrkB.T1. Differences were compared for statistical significance using Student’s t‐test and Mann‐Whitney test.Results5 consecutive days of 1 hour restraint caused a significant delay in WGTT of adult C57/BL6 SID mice, when compared to controls (Table 1). DEX caused a significant delay in WGTT, when compared to control mice (Table 1). DEX treatment caused a significant reduction in BDNF levels (Table 1). TrkB.T1‐V5 mice show presence of TrkB.T1 on adult enteric neurons (Fig 1). A single hour of restraint caused a significant delay in WGTT in adult T1 KO mice, when compared with littermate T1 Het mice (Table 1).DiscussionRestraint stress and DEX caused similar delay in gut transit in wildtype mice, and since DEX decreased gut BDNF levels, we infer that stress‐induced increase in glucocorticoid signaling delayed gut transit by suppressing enteric BDNF levels. Increased susceptibility of T1 KO mice to SID highlights the important role of the truncated TrkB.T1 receptor in maintenance of normal gut motility during acute and moderate stress. Thus, our data implicates altered BDNF‐TrkB.T1 signaling in the etiology of Stress Induced Dysmotility.

Enteric Glial Cells in Immunological Disorders of the Gut.

Enteric glial cells (EGCs) are one of the major cell types of neural crest lineage distributed in the gastrointestinal tract. EGCs represent an integral part of the enteric nervous system (ENS) and significantly outnumber ENS neurons. Studies have suggested that EGCs would exert essential roles in supporting the survival and functions of the ENS neurons. Notably, recent evidence has begun to reveal that EGCs could possess multiple immune functions and thereby may participate in the immune homeostasis of the gut. In this review article, we will summarize the current evidence supporting the potential involvement of EGCs in several important immunological disorders, including inflammatory bowel disease, celiac disease, and autoimmune enteropathy. Further, we highlight critical questions on the immunological aspects of EGCs that warrant future research attention.

How to Heal the Gut's Brain: Regeneration of the Enteric Nervous System.

The neural-crest-derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS disorders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed understanding of how regeneration is regulated on a cellular and molecular level in animal models with both high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

Protecting your gut feelings: How intestinal infections keep things moving

Neurons of the enteric nervous system (ENS) have limited regenerative capacity, and damage to these cells can cause neuropathies. In a recent issue of Cell, Ahrends etal. (2021) demonstrate that muscularis macrophages integrate distinct signals from diverse intestinal infections to protect ENS neurons from subsequent pathogenic insult.

ZMIZ1-associated neurodevelopmental disorder and Hirschsprung disease

De novo mutations in the gene encoding transcription factor ZMIZ1 , located on chromosome 10q22, were recently found to be associated with a novel neurodevelopmental syndrome [1]. In this case report we present a patient with developmental delay and Hirschsprung disease, who carries a de novo mutation in ZMIZ1 . Utilizing public gene expression data from mouse we confirm that ZMIZ1 is indeed expressed in progenitors of the enteric nervous system (ENS) as well as in a subpopulation of ENS neurons in the adult mouse and based on this we then propose that ZMIZ1 is a novel putative risk gene for HD.

Degenerasi dan nekrosis pada neuron penyusun sistem saraf enterik di usus halus dan usus besar tikus yang diinjeksi paraquat dichloride

&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Objective: &lt;/strong&gt;In Parkinson's disease (PD) patients, there is a disruption in the function of catecholaminergic neurons in Enteric nervous system (SSE) with some symtoms: constipations and diarrhea. Paraquat dichloride (PQ) is a neurotoxic herbicide which is thought to induce PD. This study aims to study the histological features of neurons in the enteric nervous system of small and large intestines injected with PQ.&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Ten rats were divided into 2 groups of 5 each. The control group was injected with distilled water and the treatment group was injected with PQ 7 mg/kg BW. The injection was given intraperitoneally, twice a week for 3 weeks with a volume of 1 ml/injection. Small intestine and large intestine were collected and processed for histological preparations in paraffin incisions, then stained with cresyl violet and immunohistochemistry using tyrosine hydroxylase antibody as a marker of catecholaminergic neurons. Intestinal histological preparations were observed under light microscope and analyzed descriptively.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Results: &lt;/strong&gt;Neurons in the small intestine and large intestine of normal group rats were observed normal, while in the treatment group some neurons were normal, but some of them became degeneration in the form of chromatolysis, also necrosis which was characterized by damage of cell membranes, karyolysis, loss of most of the Nissl bodies, and decreased numbers of catecholaminergic neurons.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Paraquat dichloride cause changes in enteric nervous system’s neuron structures in the form of degeneration, necrosis, and a decrease in the number of catecholaminergic neurons in the small intestine and large intestine.&lt;/p&gt;