Online first
Original article
Published online: 2023-12-05

open access

Page views 272
Article views/downloads 156
Get Citation

Connect on Social Media

Connect on Social Media

Effect of different glyphosate doses on the chemical coding of neurons of the enteric nervous system of the porcine descending colon

Michał Bulc1, Jarosław Całka1, Barbara Jana2, Katarzyna Palus1
Pubmed: 38078736

Abstract

Background: Neurons of the enteric nervous system are characterised by high neuronal plasticity, with their number likely to change in response to various endogenous and exogenous substances.

Materials and methods: Fifteen sexually immature gilts divided into 3 groups were used: control — animals receiving empty gelatin capsules; G1 — animals receiving a low dose of glyphosate — 0.05 mg/kg bw/day; G2 — animals receiving a higher dose of glyphosate—0.5 mg/kg/day in gelatin capsules orally for 28 days. Frozen sections were then subjected to the procedure of double immunofluorescent staining.

Results: With low-dose supplementation, no effect on the SP- and CART-positive neuron population was observed. However, a reduction in the number of VAChT-positive neurons in the internal submucosal plexus was described, while the number of CGRP-positive neurons increased in all enteric plexuses. In response to a high glyphosate dose, the quantitative variability of the neurons was significantly more pronounced than that for a low dose. There was an increase in the number of SP- and CGRP-positive neurons and a decrease in the number of VAChT-positive neurons in both the myenteric plexus and the submucosal plexuses. The response of CART-positive neurons was the weakest, as a high dose of glyphosate led to an increase in the number of neurons only in the myenteric plexus.

Conclusions: The above data show that glyphosate is an exogenous substance that affects neuronal populations of the enteric nervous system, in this case, the descending colon.

Article available in PDF format

View PDF Download PDF file

References

  1. Arvidsson U, Riedl M, Elde R, et al. Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker for cholinergic neurons in the central and peripheral nervous systems. J Comp Neurol. 1997; 378(4): 454–467.
  2. Azzouz LL, Sharma S. Physiology, Large Intestine. StatPearls Publishing, Treasure Island (FL) 2023.
  3. Brunsson I, Fahrenkrug J, Jodal M, et al. Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine. J Physiol. 1995; 483 ( Pt 3)(Pt 3): 727–734.
  4. Brzozowska M, Całka J. Acetylsalicylic acid supplementation affects the neurochemical phenotyping of porcine duodenal neurons. Int J Mol Sci. 2023; 24(12).
  5. Bulc M, Całka J, Palus K. Effect of streptozotocin-inducted diabetes on the pathophysiology of enteric neurons in the small intestine based on the porcine diabetes model. Int J Mol Sci. 2020; 21(6).
  6. Bulc M, Gonkowski S, Całka J. Expression of cocaine and amphetamine regulated transcript (CART) in the porcine intramural neurons of stomach in the course of experimentally induced diabetes mellitus. J Mol Neurosci. 2015; 57(3): 376–385.
  7. Bulc M, Palus K, Całka J, et al. Changes in Immunoreactivity of Sensory Substances within the Enteric Nervous System of the Porcine Stomach during Experimentally Induced Diabetes. J Diabetes Res. 2018; 2018: 4735659.
  8. Calka J. Increased expression of CART, nNOS, VIP, PACAP, SP and GAL in enteric neurons of the porcine stomach prepyloric region following hydrochloric acid infusion. Folia Histochem Cytobiol. 2019; 57(4): 179–187.
  9. Cathenaut L, Schlichter R, Hugel S, et al. Inhibitory interneurons with differential plasticities at their connections tune excitatory-inhibitory balance in the spinal nociceptive system. Pain. 2022; 163(5): e675–e688.
  10. Duke SO. Perspectives on transgenic, herbicide-resistant crops in the United States almost 20 years after introduction. Pest Manag Sci. 2015; 71(5): 652–657.
  11. Duke SO. The history and current status of glyphosate. Pest Manag Sci. 2018; 74(5): 1027–1034.
  12. Fehér E, Altdorfer K. [Neuroimmunomodulation in the mucosa of the alimentary tract]. Orv Hetil. 2020; 161(35): 1436–1440.
  13. Ferreira NGC, da Silva KA, Guimarães AT, et al. Hotspots of soil pollution: possible glyphosate and aminomethylphosphonic acid risks on terrestrial ecosystems and human health. Environ Int. 2023; 179: 108135.
  14. Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst. 2000; 81(1-3): 87–96.
  15. Furness JB, Stebbing MJ. The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems. Neurogastroenterol Motil. 2018; 30(2).
  16. Furness JB. Integrated neural and endocrine control of gastrointestinal function. Adv Exp Med Biol. 2016; 891: 159–173.
  17. Godlewski J, Kmiec Z. Colorectal cancer invasion and atrophy of the enteric nervous system: potential feedback and impact on cancer progression. Int J Mol Sci. 2020; 21(9).
  18. Gonkowski S, Gajęcka M, Makowska K. Mycotoxins and the enteric nervous system. Toxins (Basel). 2020; 12(7).
  19. Gonkowski S, Kamińska B, Landowski P, et al. Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide - like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon. Histol Histopathol. 2013; 28(7): 851–858.
  20. Gonzalez LM, Moeser AJ, Blikslager AT. Porcine models of digestive disease: the future of large animal translational research. Transl Res. 2015; 166(1): 12–27.
  21. Hay DL, Garelja ML, Poyner DR, et al. Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. Br J Pharmacol. 2018; 175(1): 3–17.
  22. Holzer P, Holzer-Petsche U. Constipation caused by anti-calcitonin gene-related peptide migraine therapeutics explained by antagonism of calcitonin gene-related peptide's motor-stimulating and prosecretory function in the intestine. Front Physiol. 2021; 12: 820006.
  23. Huang R, Wu JH, Wang SL. [Effect of moxibustion on colonic mucosal injury and expression of CGRP positive nerve fibers of distal colonic mucosa in ulcerative colitis mice]. Zhongguo Zhen Jiu. 2021; 41(10): 1127–1134.
  24. Inoue R, Nishimune H. Neuronal plasticity and age-related functional decline in the motor cortex. Cells. 2023; 12(17): 2142.
  25. Jakob MO, Kofoed-Branzk M, Deshpande D, et al. An integrated view on neuronal subsets in the peripheral nervous system and their role in immunoregulation. Front Immunol. 2021; 12: 679055.
  26. Kaleczyc J, Klimczuk M, Franke-Radowiecka A, et al. The distribution and chemical coding of intramural neurons supplying the porcine stomach - the study on normal pigs and on animals suffering from swine dysentery. Anat Histol Embryol. 2007; 36(3): 186–193.
  27. Kwiatkowski P, Godlewski J, Kieżun J, et al. Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues. Oncol Lett. 2016; 12(5): 3323–3329.
  28. Le Berre C, Naveilhan P, Rolli-Derkinderen M. Enteric glia at center stage of inflammatory bowel disease. Neurosci Lett. 2023; 809: 137315.
  29. Li FJ, Zou YY, Cui Yi, et al. Calcitonin gene-related peptide is a promising marker in ulcerative colitis. Dig Dis Sci. 2013; 58(3): 686–693.
  30. Li ZS, Furness JB. Immunohistochemical localisation of cholinergic markers in putative intrinsic primary afferent neurons of the guinea-pig small intestine. Cell Tissue Res. 1998; 294(1): 35–43.
  31. Makowska K, Fagundes KRC, Gonkowski S. Influence of bisphenol A and its analog bisphenol S on cocaine- and amphetamine-regulated transcript peptide-positive enteric neurons in the mouse gastrointestinal tract. Front Mol Neurosci. 2023; 16: 1234841.
  32. Makowska K, Gonkowski S, Zielonka L, et al. T2 toxin-induced changes in cocaine- and amphetamine-regulated transcript (CART)-like immunoreactivity in the enteric nervous system within selected fragments of the porcine digestive tract. Neurotox Res. 2017; 31(1): 136–147.
  33. Makowska K, Gonkowski S. Changes caused by bisphenols in the chemical coding of neurons of the enteric nervous system of mouse stomach. Int J Environ Res Public Health. 2023; 20(6).
  34. Makowska K, Gonkowski S. The influence of inflammation and nerve damage on the neurochemical characterization of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) neurons in the enteric nervous system of the porcine descending colon. Int J Mol Sci. 2018; 19(2).
  35. Makowska K, Lepiarczyk E, Gonkowski S. The comparison of the influence of bisphenol a (BPA) and its analogue bisphenol s (BPS) on the enteric nervous system of the distal colon in mice. Nutrients. 2022; 15(1).
  36. Makowska K, Rytel L, Lech P, et al. Cocaine- and amphetamine-regulated transcript (CART) peptide in the enteric nervous system of the porcine esophagus. C R Biol. 2018; 341(6): 325–333.
  37. Mishra A, Lal G. Neurokinin receptors and their implications in various autoimmune diseases. Curr Res Immunol. 2021; 2: 66–78.
  38. Myers JP, Antoniou MN, Blumberg B, et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health. 2016; 15: 19.
  39. Palus K, Bulc M, Całka J. Changes in VIP-, SP- and CGRP- like immunoreactivity in intramural neurons within the pig stomach following supplementation with low and high doses of acrylamide. Neurotoxicology. 2018; 69: 47–59.
  40. Palus K, Bulc M, Całka J. Effect of acrylamide supplementation on the CART-, VAChT-, and nNOS-Immunoreactive nervous structures in the porcine stomach. Animals (Basel). 2020; 10(4).
  41. Palus K, Bulc M, Całka J. Glyphosate affects the neurochemical phenotype of the intramural neurons in the duodenum in the pig. Neurogastroenterol Motil. 2023; 35(3): e14507.
  42. Rytel L, Palus K, Całka J. Co-expression of PACAP with VIP, SP and CGRP in the porcine nodose ganglion sensory neurons. Anat Histol Embryol. 2015; 44(2): 86–91.
  43. Rytel L, Wojtkiewicz J, Snarska A, et al. Changes in the neurochemical characterization of enteric neurons in the porcine duodenum after administration of low-dose salmonella enteritidis lipopolysaccharides. J Mol Neurosci. 2021; 71(8): 1556–1566.
  44. Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020; 17(6): 338–351.
  45. Sundler F, Ekblad E, Håkanson R. Occurrence and distribution of substance P- and CGRP-containing nerve fibers in gastric mucosa: species differences. Adv Exp Med Biol. 1991; 298: 29–37.
  46. Szymanska K, Gonkowski S. Bisphenol A-Induced changes in the enteric nervous system of the porcine duodenum. Neurotoxicology. 2018; 66: 78–86.
  47. Szymanska K, Gonkowski S. Neurochemical characterization of the enteric neurons within the porcine jejunum in physiological conditions and under the influence of bisphenol A (BPA). Neurogastroenterol Motil. 2019; 31(6): e13580.
  48. Makowska K, Obremski K, Gonkowski S. The impact of T-2 toxin on vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nerve structures in the wall of the porcine stomach and duodenum. Toxins (Basel). 2018; 10(4).
  49. Uesaka T, Young HM, Pachnis V, et al. Development of the intrinsic and extrinsic innervation of the gut. Dev Biol. 2016; 417(2): 158–167.
  50. Wierup N, Gunnarsdóttir A, Ekblad E, et al. Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands. BMC Neurosci. 2007; 8: 51.
  51. Ziegler A, Gonzalez L, Blikslager A. Large animal models: the key to translational discovery in digestive disease research. Cell Mol Gastroenterol Hepatol. 2016; 2(6): 716–724.