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Glyphosate is the active ingredient of glyphosate-based herbicides and the most commonly used pesticide in the world. The goal of the present study was to verify whether low doses of glyphosate (equivalent to the environmental exposure) evoke changes in galanin expression in intramural neurons in the small intestine in pigs and to quantitatively determine changes in the level of galanin receptor encoding mRNA (GALR1, GALR2, GALR3) in the small intestine wall. The experiment was conducted on 15 sexually immature gilts divided into three study groups: control (C)—animals receiving empty gelatin capsules; experimental 1 (G1)—animals receiving a low dose of glyphosate (0.05 mg/kg b.w./day); experimental 2 (G2)—animals receiving a higher dose of glyphosate (0.5 mg/kg b.w./day) orally in gelatine capsules for 28 days. Glyphosate ingestion led to an increase in the number of GAL-like immunoreactive intramural neurons in the porcine small intestine. The results of RT-PCR showed a significant increase in the expression of mRNA, which encodes the GAL-receptors in the ileum, a decreased expression in the duodenum and no significant changes in the jejunum. Additionally, intoxication with glyphosate increased the expression of SOD2-encoding mRNA in the duodenum and decreased it in the jejunum and ileum, but it did not affect SOD1 expression. The results suggest that it may be a consequence of the cytotoxic and/or neurotoxic properties of glyphosate and/or its ability to induce oxidative stress. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine disruptor commonly used in the production of plastics. Due to its relatively well-known harmful effects on living organisms, BPA is often replaced by its various analogues. One of them is bisphenol S (BPS), widely used in the plastics industry. Until recently, BPS was considered completely safe, but currently, it is known that it is not safe for various internal organs. However, knowledge about the influence of BPS on the nervous system is scarce. Therefore, the aim of this study was to investigate the influence of two doses of BPA and BPS on the enteric nitrergic neurons in the CD1 strain mouse stomach using the double-immunofluorescence technique. The study found that both substances studied increased the number of nitrergic neurons, although changes under the impact of BPS were less visible than those induced by BPA. Therefore, the obtained results, for the first time, clearly indicate that BPS is not safe for the innervation of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

This study analyzed severe acute endometritis action on myometrial density and distribution of protein gene product (PGP)9.5- and calcitonin gene-related peptide (CGRP)-like immunoreactive nerve fibers and calcitonin receptor-like receptor (CLR) expression, and on CGRP receptor (CGRPR) participation in uterine contractility in pigs. E. coli suspension (E. coli group) or saline (SAL group) were injected into the uteri, or only laparotomy was performed (CON group). In the E. coli group myometrium, a lack of significant changes in PGP9.5 and CGRP innervation patterns and increased CLR protein level were revealed. In all groups, compared to the pretreatment period, human αCGRP increased amplitude in the myometrium, while reducing it in endometrium/myometrium. In the E. coli group endometrium/myometrium, human αCGRP lowered amplitude vs other groups. Human αCGRP reduced frequency in CON and SAL groups and enhanced it in the E. coli group endometrium/myometrium. The frequency in E. coli group increased vs other groups. CGRPR antagonist, human αCGRP8–37, reversed (CON, SAL groups) and eliminated (E. coli group) the rise in human αCGRP-induced myometrial amplitude. In endometrium/myometrium, human αCGRP8–37 abolished (CON group) and reversed (SAL group) a decrease in frequency, and reduced the rise in frequency (E. coli group) caused by human αCGRP. Collectively, in the myometrium, endometritis did not change PGP9.5 and CGRP innervation patterns and enhanced CLR protein level. CGRPR also mediated in CGRP action on inflamed uterus contractility. [ABSTRACT FROM AUTHOR]

Uterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility. [ABSTRACT FROM AUTHOR]

In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of our study was to localize and define immunocytochemical characteristic of the dorsal motor nucleus of the vagus (DMX) neurons projecting to the porcine stomach prepyloric region in the physiological state and after gastric partial resection. To identify the stomach-projecting perikarya, the neuronal retrograde tracer-Fast Blue (FB) was injected into the studied region of control and resection group (RES). In the RES group, on 22nd day after FB injection, the partial resection of the stomach region previously injected with FB was performed. Sections were immunostained with 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 DMX of control and RES group, the stomach-projecting perikarya were found in the entire extent of the nucleus bilaterally. Within control animals, 30.08 ± 1.97 % of the gastric DMX perikarya expressed PACAP, while other substances were found only in the neuronal fibers. In the RES group DMX, PACAP was found in 45.58 ± 2.2 %, VIP in 28.83 ± 3.63 %, NOS in 21.22 ± 3.32 %, and GAL in 5.67 ± 1.49 % of the FB-labeled gastric perikarya. Our data implicate PACAP, VIP, NOS, and GAL as neuronal survival promoting substances and the CART-, LENK-, SP- NOS-, and GAL-immunoreactive processes in control of the gastric vagal neurons in the pig. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the influence of estradiol-17β (E) overdose on the number and distribution of ovarian parasympathetic neurons in the paracervical ganglion (PCG) in adult pigs. To identify the neurons innervating gonads on day 3 of the estrous cycle, the ovaries of both the control and experimental gilts were injected with retrograde neuronal tracer Fast Blue. From next day to the expected day 20 of the second studied cycle, experimental gilts were injected with E, while control gilts received oil. The PCG were then collected and processed for double-labeling immunofluorescence. Injections of E increased the E level in the peripheral blood approximately four- to fivefold and reduced the following in the PCG: the total number of Fast Blue-positive neurons; the number of perikarya in the lateral part of the PCG; the numbers of vesicular acetylcholine transporter (VAChT)/somatostatin, VAChT/vasoactive intestinal polypeptide (VIP), VAChT/neuronal isoform of nitric oxide synthase, VAChT/VIP, VAChT/dopamine β-hydroxylase (DβH), VAChT/VIP, and VAChT/DβH perikarya; and the total number of perikarya expressing estrogen receptors (ERs) subtype α and/or β. In summary, long-term E treatment of adult gilts downregulates the population of both cholinergic and ERs expressing the PCG ovary-projecting neurons. Our results suggest that elevated E levels occurring during pathological states may regulate gonadal function(s) by affecting ovary-supplying neurons. [ABSTRACT FROM AUTHOR]

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several urinary bladder dysfunction clinical trials. The aim of this study was to establish the effect of intravesical administration of RTX and TTX on neuropeptides Y (NPY) and tyrosine hydroxylase (TH) relationship in the paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. TH is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA) and is used as a marker of catecholaminergic neurons. NPY augments the vasoconstrictor effects of noradrenergic neurons, and is involved in pathophysiological processes as a neuromodulator. To identify the PCG neurons supplying urinary bladder Fast Blue (FB) was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in control group 64.08 % of FB-positive PCG neurons contain NPY and 4.25 % TH. Intravesical infusion of RTX resulted upregulation of the NPY-IR neurons to 82.97 % and TH-IR to 43.78 %. Also administration of TTX induced further increase number of TH-IR neurons to 77.49 % but induced decrease number of NPY-IR neurons to 57.45 %. Both neurotoxins affect chemical coding of the PCG neural somata supplying urinary bladder, but the effects of their action are different. This results shed light on possible involvement of RTX and TTX on curing tissue, and potentially could help us to broaden our neurourological armamentarium. [ABSTRACT FROM AUTHOR]

This study reports on changes in the pituitary adenylate cyclase-activating peptide 27-like immunoreactive (PACAP-27-LI) nerve structures of the enteric nervous system (ENS) in the porcine descending colon, caused by chemically induced inflammation, nerve injury, and proliferative enteropathy (PE), which is a 'natural' inflammation of the porcine digestive tract. The distribution pattern of PACAP-27-LI structures was studied using the immunofluorescence technique in the circular muscle layer, enteric plexuses (i.e., myenteric plexus (MP), outer submucous plexus (OSP), and inner submucous plexus (ISP)), and in the mucosal layer. Under physiological conditions, PACAP-27-LI perikarya have been shown to constitute 4.04 ± 0.66, 6.66 ± 0.77, and 11.19 ± 0.74 % in the MP, OSP, and ISP, respectively. Changes in PACAP-27 immunoreactivity depended on the pathological factor studied. The numbers of the PACAP-27-LI perikarya amounted to 12.26 ± 1.43, 12.28 ± 0.79, and 21.13 ± 1.19 % in chemically induced colitis, 17.83 ± 0.88, 9.03 ± 1.05, and 20.72 ± 1.35 % during PE and 10.65 ± 0.82, 6.88 ± 1.04, and 14.04 ± 1.09 % after axotomy in MP, OSP, and ISP, respectively. All of the studied processes generally resulted in an increase in the number of PACAP-27-LI nerve fibers in the circular muscle and mucosal layers. The obtained results suggest that PACAP-27-LI nerve structures of ENS may participate in various pathological states within the porcine descending colon, and their functions probably depend on the type of pathological factor. [ABSTRACT FROM AUTHOR]