Influence of Acrylamide Administration on the Neurochemical Characteristics of Enteric Nervous System (ENS) Neurons in the Porcine Duodenum

Abstract

The digestive tract, especially the small intestine, is one of the main routes of acrylamide absorption and is therefore highly exposed to the toxic effect of acrylamide contained in food. The aim of this experiment was to elucidate the effect of low (tolerable daily intake—TDI) and high (ten times higher than TDI) doses of acrylamide on the neurochemical phenotype of duodenal enteric nervous system (ENS) neurons using the pig as an animal model. The experiment was performed on 15 immature gilts of the Danish Landrace assigned to three experimental groups: control (C) group—pigs administered empty gelatine capsules, low dose (LD) group—pigs administered capsules with acrylamide at the TDI dose (0.5 μg/kg body weight (b.w.)/day), and the high dose (HD) group—pigs administered capsules with acrylamide at a ten times higher dose than the TDI (5 μg/kg b.w./day) with a morning feeding for 4 weeks. Administration of acrylamide, even in a low (TDI) dose, led to an increase in the percentage of enteric neurons immunoreactive to substance P (SP), calcitonin gene-related peptide (CGRP), galanin (GAL), neuronal nitric oxide synthase (nNOS), and vesicular acetylcholine transporter (VACHT) in the porcine duodenum. The severity of the changes clearly depended on the dose of acrylamide and the examined plexus. The obtained results suggest the participation of these neuroactive substances in acrylamide-inducted plasticity and the protection of ENS neurons, which may be an important line of defence from the harmful action of acrylamide.

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

“…Interesting findings gained in the present investigation concerned the impact of BPA on VIP-positive nervous structures—namely, an increase in the number of nerve cells immunoreactive to VIP in the myenteric ganglia, as well as VIP-positive intramuscular and intramucosal nerves with a simultaneous decrease in the number of cells positive for VIP in the submucous ganglia has been noted. These observations are different from results obtained in the previous studies, in which the increase of VIP-positive enteric nervous was noted in the intestine both under the impact of BPA and other pathological states [ 12 , 13 , 22 , 24 , 30 ], which was explained by the fact that VIP is involved in neuroprotective processes through modulation of the balance between anti- and pro-inflammatory cytokines [ 24 , 31 , 32 ].…”

“…Namely, during this investigation in all parts of the gastric wall, administration of BPA resulted in the increase in the number of nervous structures positive for GAL, which influences NK cells and modulates the synthesis of IFN-γ, IL-18, and IL-12/23 [ 53 ] and to CART, which in the nervous system reduces the expression of inflammatory factors [ 47 ]. Mechanisms in which the influence of the same external pathological factor causes an increase in the number of neurons containing both anti- and pro-inflammatory substances is not clear, but similar reaction of the ENS on toxic and pathological stimuli has been also reported in the previous investigations [ 24 , 31 , 54 ]. Moreover, it is public knowledge that BPA may cause similar alterations in the autonomic nervous system supplying the other internal organs [ 6 , 55 ].…”

“…The enteric neuronal cells show a high degree of diversity in terms of morphology, function, and neurochemical characterization [ 20 , 23 ]. They take part in regulation of the functions of the GI tract not only in physiology, but also in adaptive reactions in order to respond to processes occurring during systemic and/or gastrointestinal diseases, as well as under the impact of toxic substances [ 12 , 20 , 21 , 24 , 25 ]. With regard to correlation between pathological gastrointestinal symptoms and changes in the ENS, knowledge about this issue is not extensive, but it is known that enteric neurons undergo changes during diarrhea, constipation, and vomiting [ 26 , 27 , 28 , 29 ].…”

Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis

“…Both treatments led to significant increases in the percentage of neurons immunoreactive to substance P (SP), CGRP, galanin, nNOS, and vesicular acetylcholine transporter (VACHT), although the high dose exerted more intense changes. In this case too, the interpretation given by the authors is that all these changes may be compensatory plastic effects in an attempt to protect neurons from damage and restore enteric neuronal homeostasis [ 194 ]. Of note, although acrylamide activates microglial cells both in vivo and in vitro, leading to the release of proinflammatory cytokines, and consequently contributing to neuronal damage [ 195 ], the involvement of enteric glial cells in enteric neuronal alterations induced by acrylamide has not been specifically evaluated yet, except for the above-mentioned study that used cocultures of intestinal myenteric neurons, smooth muscle cells, and glia, and did not show any acrylamide-induced alterations in this last cell type [ 188 ].…”

Neuropeptidergic Control of Feeding: Focus on the Galanin Family of Peptides

“…In this animal model, studies have been carried out on the influence of certain substances present in food or in food containers on the enteric system and especially on the expression of diverse neuropeptides, among them, GAL. Acrylamide, which exerts toxic effects in rodents and humans, is contained in food (e.g., coffee, fries, chips) and absorbed mainly in the small intestine which is directly exposed to its toxic effect [ 79 ]. Daily administration of low (0.5 μg/kg) and high (5 μg/kg) doses of acrylamide to pigs for four weeks produced changes in the neurochemical characteristics of the neurons located in the duodenum and belonging to the enteric nervous system [ 79 ].…”