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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.    Abstract  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.

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