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

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.

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 461 ◽  
Author(s):  
Sławomir Gonkowski ◽  
Magdalena Gajęcka ◽  
Krystyna Makowska

Mycotoxins are secondary metabolites produced by various fungal species. They are commonly found in a wide range of agricultural products. Mycotoxins contained in food enter living organisms and may have harmful effects on many internal organs and systems. The gastrointestinal tract, which first comes into contact with mycotoxins present in food, is particularly vulnerable to the harmful effects of these toxins. One of the lesser-known aspects of the impact of mycotoxins on the gastrointestinal tract is the influence of these substances on gastrointestinal innervation. Therefore, the present study is the first review of current knowledge concerning the influence of mycotoxins on the enteric nervous system, which plays an important role, not only in almost all regulatory processes within the gastrointestinal tract, but also in adaptive and protective reactions in response to pathological and toxic factors in food.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Krystyna Makowska ◽  
Piotr Lech ◽  
Mariusz Majewski ◽  
Andrzej Rychlik ◽  
Slawomir Gonkowski

AbstractBisphenol A (BPA) is used in the production of plastics approved for contact with feed and food. Upon entering living organisms, BPA, as a potent endocrine disruptor, negatively affects various internal organs and regulatory systems, especially in young individuals. Although previous studies have described the neurotoxic effects of BPA on various tissues, it should be underlined that the putative influence of this substance on the chemical architecture of the urinary bladder intrinsic innervation has not yet been studied. One of the most important neuronal substances involved in the regulation of urinary bladder functions is vasoactive intestinal polypeptide (VIP), which primarily participates in the regulation of muscular activity and blood flow. Therefore, this study aimed to determine the influence of various doses of BPA on the distribution pattern of VIP-positive neural structures located in the wall of the porcine urinary bladder trigone using the double-immunofluorescence method. The obtained results show that BPA influence leads to an increase in the number of both neurons and nerve fibres containing VIP in the porcine urinary bladder trigone. This may indicate that VIP participates in adaptive processes of the urinary bladder evoked by BPA.


2020 ◽  
Vol 21 (22) ◽  
pp. 8743 ◽  
Author(s):  
Kamila Szymańska ◽  
Krystyna Makowska ◽  
Jarosław Całka ◽  
Sławomir Gonkowski

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.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  

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.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 780
Author(s):  
Krystyna Makowska ◽  
Slawomir Gonkowski

Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.


2018 ◽  
Vol 19 (10) ◽  
pp. 2962 ◽  
Author(s):  
Liliana Rytel

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.


2017 ◽  
Vol 114 (18) ◽  
pp. E3709-E3718 ◽  
Author(s):  
Subhash Kulkarni ◽  
Maria-Adelaide Micci ◽  
Jenna Leser ◽  
Changsik Shin ◽  
Shiue-Cheng Tang ◽  
...  

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.


2021 ◽  
Vol 12 (1) ◽  
pp. 3-8
Author(s):  
М. М. Kushch ◽  
D. S. Makhotyna ◽  
I. A. Fesenko ◽  
M. M. Savenko ◽  
A. Y. Ulianytska

As evidenced by the publications of recent years, contrary to the existing dogma about the immutability of the state of the enteric nervous system during the postnatal period of ontogenesis, the population of intestinal neurons is a dynamic formation, decreasing with age and changing due to the action of environmental factors. The current article presents the results of study of the microscopic structure of the nerve plexus of the muscular membrane of the enteric nervous system of domestic ducks (Anas platyrhynchos domesticus) of the black white–breasted breed, of nine age groups of 1–365 days of age. The topography, number, area of nerve nodes, as well as the density of neurons in them were determined on transverse sections of the duodenum, jejunum, ileum, caecum and rectum. For the purpose of a generalized assessment of the morphofunctional state of the nerve plexuses, two parameters were determined: the average age indicator of the gut and intestines. The average age indicator of a certain structure of each intestine was determined as the arithmetical average of its nine age indicators. The average age indicator of a certain gut structure was determined as the arithmetic average of the average age indicator of the structure of all five intestines. It has been established that the nerve plexus of the muscular membrane (myenteric, plexus Auerbachi) of the gut of domestic ducks, in contrast to mammals, is not located between the layers of the muscular membrane, but in its outer layer. On a transverse section of the gut wall, the myenteric ganglia and cords that connect have a predominantly elliptical shape. Despite a significant increase with age in the diameter and thickness of the gut wall, the total number of myenteric ganglia changed little, increasing or decreasing with varying degrees of reliability relative to the previous age. In the gut of ducks, during the first year of the postnatal period of ontogenesis, the smallest number of myenteric ganglia was found in the cecum, and the largest – in the ileum. The general pattern of the dynamics of the size of the myenteric ganglia of the gut of ducks was an increase in their area with age. Moreover, this indicator reached the greatest value at different ages of ducks: at 30 days of age in the ileum and cecum, at 180 days of age – in the rectum and at 365 days of age – in the duodenum. The smallest area of the myenteric ganglia was found in the jejunum, and the largest – in the duodenum and ileum. The smallest number of neurons in the ganglion was found in the cecum, and the largest – in the rectum, the lowest density of neurons in the ganglion was found in the cecum, and the largest – in the jejunum. The general quantitative pattern of neurons in the ganglion was the decrease in their density with age. Changes in the morphometric parameters of the ganglia of the nerve plexus of the muscular membrane of the ducks’ gut indicate the plasticity of the enteric nervous system, its ability to dynamically respond to the action of factors of the internal and external environment. It is promising to study the state of the submucous nerve plexus, as well as the cellular composition of the population of neurons of the enteric nervous system of domestic and wild poultry.


Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2253
Author(s):  
Miguel Gonzalez Acera ◽  
Marvin Bubeck ◽  
Fabrizio Mascia ◽  
Leonard Diemand ◽  
Gregor Sturm ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.


2017 ◽  
Vol 642 ◽  
pp. 59-65 ◽  
Author(s):  
Xiaolei Han ◽  
Shi Tang ◽  
Lingling Dong ◽  
Lin Song ◽  
Yi Dong ◽  
...  

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