Prolonged Acetylsalicylic-Acid-Supplementation-Induced Gastritis Affects the Chemical Coding of the Stomach Innervating Vagal Efferent Neurons in the Porcine Dorsal Motor Vagal Nucleus (DMX)

Abstract

The main goal of our research was to study the possible alterations of the chemical coding of the dorsal motor vagal nucleus (DMX) neurons projecting to the porcine stomach prepyloric region following prolonged acetylsalicylic acid supplementation. Fast Blue (FB) was injected into the studied area of the stomach. Since the seventh day following the FB injection, acetylsalicylic acid (ASA) was given orally to the experimental gilts. All animals were euthanized on the 28th day after FB injection. Medulla oblongata sections were then processed for double-labeling immunofluorescence for choline acetyltransferase (ChAT), pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), galanin (GAL), substance P (SP), leu enkephalin (LENK), and cocaine- and amphetamine-regulated transcript (CART). In the control DMX, only PACAP was observed in 30.08 ± 1.97 % of the FB-positive neurons, while VIP, NOS, GAL, SP, LENK, and CART were found exclusively in neuronal processes running between FB-labeled perikarya. In the ASA DMX, PACAP was revealed in 49.53 ± 5.73 % of traced vagal perikarya. Moreover, we found de novo expression of VIP in 40.32 ± 7.84 %, NOS in 25.02 ± 6.08 %, and GAL in 3.37 ± 0.85 % of the FB-labeled neurons. Our results suggest that neuronal PACAP, VIP, NOS, and GAL are mediators of neural response to aspirin-induced stomach inflammatory state.

Neurochemical Plasticity of nNOS-, VIP- and CART-Immunoreactive Neurons Following Prolonged Acetylsalicylic Acid Supplementation in the Porcine Jejunum

“…In turn, the populations of nNOS-expressing nerve cells in both the outer and the inner submucous plexuses were also significantly decreased but to a lesser extent than in the MP. Reduction of nNOS-IR enteric neurons was previously observed during diabetes [44], Chagas' disease [45], Hirschsprung's disease [46], as well as ischemia [22]. In contrast, an increase in the proportions of nNOS-IR enteric intramural neurons was found in the swine small intestine during proliferative enteropathy [47], ileitis [22], inflammatory bowel disease (IBD) [48].…”

“…To date, there are only a few studies focusing on the distribution of nNOS in the porcine ENS, particularly in the jejunum. Most studies assess changes in the expression of nNOS in the stomach [45,46], while modifications in the small intestine are poorly described. Our data showing the relatively large population of nNOS-positive enteric neurons confirms the previously described roles of NO in the regulation of physiological processes within the GIT, as well as during pathological stages.…”

Increased expression of CART, nNOS, VIP, PACAP, SP and GAL in enteric neurons of the porcine stomach prepyloric region following hydrochloric acid infusion

“…Available data show that PACAP stimulates bicarbonate secretion in the duodenum [38,51] as well as gastric acid secretion in the stomach [16]. Our previous findings revealed in aspirin-evoked pig model of stomach inflammation increased expression of PACAP as well as de novo expression of VIP, NOS and GAL in numerous stomach-supplying perikarya located in the dorsal motor vagal nucleus (DMX) [52]. Thus, activation of the parasympathetic stomach supplying DMX-located neurons triggers interneuronal signaling mechanisms which promote the release of the neurotransmitters into the gastric submucosal space.…”

XiangshaLiujunzi decoction alleviates the symptoms of functional dyspepsia by regulating brain–gut axis and production of neuropeptides

“…Hormonal signals from the periphery are integrated with high brain centre signals to regulate appetite and control energy expenditure. The release of gut hormones, such as ghrelin, CCK and VIP, regulates the brain–gut axis using hormonal signals [ 16 , 17 , 20 , 26 ].…”

“…VIP, a 28-amino acid neuropeptide, is distributed in central and peripheral neurons; this neuropeptide is involved in many physiological intestinal functions, such as motility regulation, secretory activity and vasodilatation, peristaltic reflex inhibition in the circular smooth muscle layer and sphincter relaxation [ 25 ]. Neuronal VIP is also a mediator of neural response to aspirin-induced stomach inflammatory state [ 26 ]. These studies demonstrated that the disorder of the brain–gut axis may be the pathogenesis of FD.…”