scholarly journals The Endocrine Disruptor Bisphenol A (BPA) Affects the Enteric Neurons Immunoreactive to Neuregulin 1 (NRG1) in the Enteric Nervous System of the Porcine Large Intestine

2020 ◽  
Vol 21 (22) ◽  
pp. 8743 ◽  
Author(s):  
Kamila Szymańska ◽  
Krystyna Makowska ◽  
Jarosław Całka ◽  
Sławomir Gonkowski
Keyword(s):  
Nervous System ◽  
Bisphenol A ◽  
Enteric Nervous System ◽  
Large Intestine ◽  
Enteric Neurons ◽  
Neuregulin 1 ◽  
Proinflammatory Activity ◽  
High Doses ◽  
High Degree ◽  
The Impact

The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin 1 (NRG1), a factor known to be involved in the assurance of normal development of the nervous system. During the study, made up using the double immunofluorescence technique, the presence of NRG1 in the ENS of the selected segment of porcine large intestine (caecum, ascending and descending colon) was observed in physiological conditions, as well as under the impact of low and high doses of bisphenol A (BPA) which is commonly used in the production of plastics. In control animals in all types of the enteric plexuses, the percentage of NRG1-positive neurons oscillated around 20% of all neurons. The administration of BPA caused an increase in the number of NRG1-positive neurons in all types of the enteric plexuses and in all segments of the large intestine studied. The most visible changes were noted in the inner submucous plexus of the ascending colon, where in animals treated with high doses of BPA, the percentage of NRG1-positive neurons amounted to above 45% of all neuronal cells. The mechanisms of observed changes are not entirely clear, but probably result from neurotoxic, neurodegenerative and/or proinflammatory activity of BPA and are protective and adaptive in nature.

scholarly journals Alterations in Galanin-Like Immunoreactivity in the Enteric Nervous System of the Porcine Stomach Following Acrylamide Supplementation

2019 ◽  
Vol 20 (13) ◽  
pp. 3345 ◽  
Author(s):  
Katarzyna Palus ◽  
Krystyna Makowska ◽  
Jarosław Całka
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Daily Intake ◽  
Enteric Neurons ◽  
Double Labelling ◽  
Recovery Processes ◽  
High Doses ◽  
Oxide Synthase ◽  
The Impact ◽  
Double Labelling Immunohistochemistry

In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), especially among young people has been noted. The present study was created to establish the impact of acrylamide supplementation, in tolerable daily intake (TDI) dose and a dose ten times higher than TDI, on the population of galanin-like immunoreactive (GAL-LI) stomach neurons in pigs. Additionally, in the present study, the possible functional co-operation of GAL with other neuroactive substances and their role in acrylamide intoxication was investigated. Using double-labelling immunohistochemistry, alterations in the expression of GAL were examined in the porcine stomach enteric neurons after low and high doses of acrylamide supplementation. Generally, upregulation in GAL-LI immunoreactivity in both myenteric and submucous plexuses was noted in all stomach fragments studied. Additionally, the proportion of GAL-expressing cell bodies simultaneously immunoreactive to vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and cocaine- and amphetamine- regulated transcript peptide (CART) also increased. The results suggest neurotrophic or/and neuroprotective properties of GAL and possible co-operation of GAL with VIP, nNOS, CART in the recovery processes in the stomach enteric nervous system (ENS) neurons following acrylamide intoxication.

scholarly journals Bisphenol A (BPA) Affects the Enteric Nervous System in the Porcine Stomach

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2445
Author(s):  
Krystyna Makowska ◽  
Sławomir Gonkowski
Keyword(s):  
Nervous System ◽  
Bisphenol A ◽  
Enteric Nervous System ◽  
Gastric Wall ◽  
Cholinergic Neurons ◽  
Double Immunofluorescence ◽  
Adaptive Processes ◽  
Living Organisms ◽  
The Impact ◽  
Myenteric Ganglia

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.

scholarly journals The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine

2021 ◽  
Vol 22 (19) ◽  
pp. 10308
Author(s):  
Krystyna Makowska ◽  
Kamila Szymańska ◽  
Jarosław Całka ◽  
Sławomir Gonkowski
Keyword(s):  
Bisphenol A ◽  
Enteric Neurons ◽  
Neuregulin 1 ◽  
Enteric Plexus ◽  
Other Substances ◽  
Intestinal Functions ◽  
Living Organisms ◽  
Oxide Synthase ◽  
The Impact ◽  
Active Substances

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.

scholarly journals Neuregulin 1 (NRG-1) as a neuronal active substance in the porcine intrahepatic nerve fibers in physiological conditions and under the influence of bisphenol A (BPA)

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Liliana Rytel ◽  
Marcelo Alarcón Lozano ◽  
Slawomir Gonkowski
Keyword(s):  
Bisphenol A ◽  
Liver Damage ◽  
Living Organism ◽  
Nerve Fibers ◽  
Neuregulin 1 ◽  
Physiological Conditions ◽  
High Doses ◽  
Oxide Synthase ◽  
The Impact ◽  
First Time

AbstractBisphenol A (BPA) is a substance commonly used in the production of plastics. Previous studies have described that it shows multidirectional harmful effects on the living organism. It is known that BPA causes liver damage, but knowledge about the roles of intrahepatic nerves in these mechanisms is extremely scanty. On the other hand, the exact roles of some neuronal substances in the nervous structures located in the liver still remain unknown. One of such substances, which is allocated a role in the stimulation of cell survival is neuregulin 1 (NRG-1). The aim of the present studies was to investigate the distribution of NRG-1 -like immunoreactive (NRG-1-LI) nerves in the liver in physiological conditions and under the influence of various doses of BPA using routine double immunofluorescence staining. The results (for the first time) show the presence of NRG-1 in the intrahepatic nerves, and co-localization of NGR-1 with neuronal isoform of nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Moreover, it has been observed that high doses of BPA increases the density of NRG-1-LI intrahepatic nerves and the degree of co-localization of NRG-1 with VIP. These observations suggest that NRG-1 located in intrahepatic nerves may play functions in processes connected with liver damage and/or regeneration under the impact of BPA.

scholarly journals Gastric Electrical Stimulation Increases The Proliferation of Interstitial Cells of Cajal and Alters Enteric Nervous System in Diabetic Rats

2020 ◽  
Author(s):  
Cai Wang ◽  
Hui Zhang ◽  
Le Zhao ◽  
Tao Gao ◽  
Xia Liu ◽  
...  
Keyword(s):  
Nervous System ◽  
Electrical Stimulation ◽  
Enteric Nervous System ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Diabetic Rats ◽  
Gastric Electrical Stimulation ◽  
Enteric Neurons ◽  
Cells Of Cajal ◽  
The Impact

Abstract Background: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. The aims of the present study were to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved.Methods: Sixty rats were randomized into the normal rats, diabetic rats (DM), diabetic rats with sham GES (DM+SGES), and three diabetic rats with GES (DM+GES1, DM+GES2 and DM+GES3). The proliferation of ICC and expressions of 5-HT2B, nNOS, CHAT, PGP9.5 and GDNF were evaluated by immunofluorescence staining or Western blot. The expressions of 5-HT in blood and tissue were determined by ELISA.Results: (1) The proliferation of ICC was hardly observed in the DM group together with the DM+SGES group but increased in the three DM+GES groups. (2) The expression of 5-HT2B was decreased in the DM group and enhanced in the DM+GES groups. Similarly, the expressions of 5-HT in the blood and distal stomach tissue were increased in the DM+GES groups. (3) Both nNOS labeled neurons and CHAT positive neurons were reduced in myenteric plexus of the DM group, while plenty of these neurons were observed the DM+GES groups. (4) The expression of GDNF protein in the diabetic rats was down-regulated, while GES increased the expression of GDNF.Conclusion: GES improves the proliferation of ICC possibly related with 5-HT/5-HT2B signal pathway, and alters enteric nervous system 52 partly though the GDNF expression.

scholarly journals Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Enteric Nervous System ◽  
Dopamine Transporter ◽  
Myenteric Plexus ◽  
Receptor Activation ◽  
D1 Receptor ◽  
Functional Changes ◽  
Neurochemical Coding ◽  
The Impact

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

scholarly journals The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

2018 ◽  
Vol 19 (10) ◽  
pp. 2962 ◽  
Author(s):  
Liliana Rytel
Keyword(s):  
Bisphenol A ◽  
Nerve Fibers ◽  
Double Immunofluorescence ◽  
Negative Effects ◽  
Protective Mechanisms ◽  
Neuregulin 1 ◽  
Small Doses ◽  
The Impact ◽  
First Time

Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2785-2796 ◽  
Author(s):  
Alan J. Burns ◽  
Jean-Marie M. Delalande ◽  
Nicole M. Le Douarin
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Enteric Nervous System ◽  
Enteric Neurons ◽  
In Ovo ◽  
Neuronal Marker ◽  
Sacral Region ◽  
Enteric Ganglia ◽  
Migration Front ◽  
Sacral Neural Crest

The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells (NCC). Within the embryonic avian gut, vagal NCC migrate in a rostrocaudal direction to form the majority of neurons and glia along the entire length of the gastrointestinal tract, whereas sacral NCC migrate in an opposing caudorostral direction, initially forming the nerve of Remak, and contribute a smaller number of ENS cells primarily to the distal hindgut. In this study, we have investigated the ability of vagal NCC, transplanted to the sacral region of the neuraxis, to colonise the chick hindgut and form the ENS in an experimentally generated hypoganglionic hindgut in ovo model. Results showed that when the vagal NC was transplanted into the sacral region of the neuraxis, vagal-derived ENS precursors immediately migrated away from the neural tube along characteristic pathways, with numerous cells colonising the gut mesenchyme by embryonic day (E) 4. By E7, the colorectum was extensively colonised by transplanted vagal NCC and the migration front had advanced caudorostrally to the level of the umbilicus. By E10, the stage at which sacral NCC begin to colonise the hindgut in large numbers, myenteric and submucosal plexuses in the hindgut almost entirely composed of transplanted vagal NCC, while the migration front had progressed into the pre-umbilical intestine, midway between the stomach and umbilicus. Immunohistochemical staining with the pan-neuronal marker, ANNA-1, revealed that the transplanted vagal NCC differentiated into enteric neurons, and whole-mount staining with NADPH-diaphorase showed that myenteric and submucosal ganglia formed interconnecting plexuses, similar to control animals. Furthermore, using an anti-RET antibody, widespread immunostaining was observed throughout the ENS, within a subpopulation of sacral NC-derived ENS precursors, and in the majority of transplanted vagal-to-sacral NCC. Our results demonstrate that: (1) a cell autonomous difference exists between the migration/signalling mechanisms used by sacral and vagal NCC, as transplanted vagal cells migrated along pathways normally followed by sacral cells, but did so in much larger numbers, earlier in development; (2) vagal NCC transplanted into the sacral neuraxis extensively colonised the hindgut, migrated in a caudorostral direction, differentiated into neuronal phenotypes, and formed enteric plexuses; (3) RET immunostaining occurred in vagal crest-derived ENS cells, the nerve of Remak and a subpopulation of sacral NCC within hindgut enteric ganglia.

scholarly journals Abnormalities of the intestinal pacemaker cells, enteric neurons, and smooth muscle in intestinal atresia

2019 ◽  
Vol 11 (03) ◽  
pp. 180-185 ◽  
Author(s):  
Radhika krishna OH ◽  
Mohammed Abdul Aleem ◽  
Geetha Kayla
Keyword(s):  
Nervous System ◽  
Small Bowel ◽  
Enteric Nervous System ◽  
Gastrointestinal Motility ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Enteric Neurons ◽  
Small Bowel Atresia ◽  
Bowel Atresia ◽  
Cells Of Cajal

Abstract BACKGROUND: Small bowel atresia is a congenital disorder that carves a substantial morbidity. Numerous postoperative gastrointestinal motility problems occur. The underlying cause of this motility disorder is still unclear. Interstitial cells of Cajal (ICC) play a major role in gastrointestinal motility. AIMS AND OBJECTIVES: To investigate the morphological changes of enteric nervous system and ICC in small bowel atresia. MATERIAL AND METHODS: Resected small bowel specimen from affected patients (n=15) were divided into three parts (proximal, distal, atretic). Standard histology and immunohistochemistry with anti C-KIT receptor antibody (CD117), calretinin and α-SMA was carried out. The density of myenteric ICCs in the proximal, atretic and distal parts was demonstrated by CD 117 while Calretinin was used for ganglion cells and nerve bundles, α-SMA highlighted muscle hypertrophy. RESULT AND CONCLUSION: The proximal and distal bowel revealed clear changes in the morphology and density of enteric nervous system and interstitial cells of Cajal..

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