open access

Vol 77, No 4 (2018)
Original article
Submitted: 2017-09-19
Accepted: 2018-02-05
Published online: 2018-03-12
Get Citation

Immunohistochemical characteristics of porcine intrahepatic nerves under physiological conditions and after bisphenol A administration

M. Thoene1, L. Rytel1, E. Dzika1, I. Gonkowski2, A. Włodarczyk1, J. Wojtkiewicz1
·
Pubmed: 29569701
·
Folia Morphol 2018;77(4):620-628.
Affiliations
  1. University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-561 Olsztyn, Poland
  2. Department of Pathophysiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland

open access

Vol 77, No 4 (2018)
ORIGINAL ARTICLES
Submitted: 2017-09-19
Accepted: 2018-02-05
Published online: 2018-03-12

Abstract

Background: The neurochemistry of hepatic nerve fibres was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A (BPA).

Materials and methods: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibres after exposure to BPA at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine and amphetamine regulated transcript (CART). Immunoreactive nerve fibres were counted in multiple sections of the liver and among multiple animals at varying exposure levels. The data was pooled and presented as mean ± standard error of the mean.

Results: It was found that all of the nerve fibres investigated showed upregulation of these neural markers after BPA exposure, even at exposure levels currently considered to be safe. These results show very dramatic increases in nerve fibres containing the above-mentioned neuropeptides and the altered neurochemical levels may be causing a range of pathophysiological states if the trend of over-expression is extrapolated to developing humans.

Conclusions: This may have serious implications for children and young adults who are exposed to this very common plastic polymer, if the same trends are occurring in humans.

Abstract

Background: The neurochemistry of hepatic nerve fibres was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A (BPA).

Materials and methods: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibres after exposure to BPA at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine and amphetamine regulated transcript (CART). Immunoreactive nerve fibres were counted in multiple sections of the liver and among multiple animals at varying exposure levels. The data was pooled and presented as mean ± standard error of the mean.

Results: It was found that all of the nerve fibres investigated showed upregulation of these neural markers after BPA exposure, even at exposure levels currently considered to be safe. These results show very dramatic increases in nerve fibres containing the above-mentioned neuropeptides and the altered neurochemical levels may be causing a range of pathophysiological states if the trend of over-expression is extrapolated to developing humans.

Conclusions: This may have serious implications for children and young adults who are exposed to this very common plastic polymer, if the same trends are occurring in humans.

Get Citation

Keywords

bisphenol A, BPA, nerve fibres, endocrine disrupting compounds, EDC, xenoestrogen, child development

About this article
Title

Immunohistochemical characteristics of porcine intrahepatic nerves under physiological conditions and after bisphenol A administration

Journal

Folia Morphologica

Issue

Vol 77, No 4 (2018)

Article type

Original article

Pages

620-628

Published online

2018-03-12

Page views

4428

Article views/downloads

1107

DOI

10.5603/FM.a2018.0027

Pubmed

29569701

Bibliographic record

Folia Morphol 2018;77(4):620-628.

Keywords

bisphenol A
BPA
nerve fibres
endocrine disrupting compounds
EDC
xenoestrogen
child development

Authors

M. Thoene
L. Rytel
E. Dzika
I. Gonkowski
A. Włodarczyk
J. Wojtkiewicz

References (61)
  1. Akash G, Kaniganti T, Tiwari NK, et al. Differential distribution and energy status-dependent regulation of the four CART neuropeptide genes in the zebrafish brain. J Comp Neurol. 2014; 522(10): 2266–2285.
  2. Barberi M, Muciaccia B, Morelli M, et al. Expression localisation and functional activity of pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal polypeptide and their receptors in mouse ovary. Reproduction. 2007; 134(2): 281–292.
  3. Barsiene J, Syvokiene J, Bjornstad A. Induction of micronuclei and other nuclear abnormalities in mussels exposed to bisphenol A, diallyl phthalate and tetrabromodiphenyl ether-47. Aquat Toxicol. 2006; 78 Suppl 1: S105–S108.
  4. Bassols A, Costa C, Eckersall PD, et al. The pig as an animal model for human pathologies: A proteomics perspective. Proteomics Clin Appl. 2014; 8(9-10): 715–731.
  5. Bharne AP, Borkar CD, Subhedar NK, et al. Differential expression of CART in feeding and reward circuits in binge eating rat model. Behav Brain Res. 2015; 291: 219–231.
  6. Becerra V, Odermatt J. Detection and quantification of traces of bisphenol A and bisphenol S in paper samples using analytical pyrolysis-GC/MS. Analyst. 2012; 137(9): 2250–2259.
  7. Beronius A, Rudén C, Håkansson H, et al. Risk to all or none? Reproduct Toxicol. 2010; 29(2): 132–146.
  8. Braun JM, Yolton K, Dietrich KN, et al. Prenatal bisphenol A exposure and early childhood behavior. Environ Health Perspect. 2009; 117(12): 1945–1952.
  9. Braun JM, Kalkbrenner AE, Calafat AM, et al. Impact of early-life bisphenol A exposure on behavior and executive function in children. Pediatrics. 2011; 128(5): 873–882.
  10. Brown DR, Timmermans JP. Lessons from the porcine enteric nervous system. Neurogastroenterol Motil. 2004; 16 Suppl 1: 50–54.
  11. 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.
  12. Carolan E, Hogan AE, Corrigan M, et al. The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression. J Clin Endocrinol Metab. 2014; 99(3): E474–E478.
  13. Celi F, Bini V, Papi F, et al. Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development. Clin Endocrinol (Oxf). 2005; 63(2): 139–145.
  14. Dabrowska H, Kopko O, Lehtonen KK, et al. An integrated assessment of pollution and biological effects in flounder, mussels and sediment in the southern Baltic Sea coastal area. Environ Sci Pollut Res Int. 2017; 24(4): 3626–3639.
  15. DeLeón M, Coveñas R, Chadi G, et al. Subpopulations of primary sensory neurons show coexistence of neuropeptides and glucocorticoid receptors in the rat spinal and trigeminal ganglia. Brain Res. 1994; 636(2): 338–342.
  16. Duong CN, Ra JS, Cho J, et al. Estrogenic chemicals and estrogenicity in river waters of South Korea and seven Asian countries. Chemosphere. 2010; 78(3): 286–293.
  17. 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.
  18. Gonkowski S, Rowniak M, Wojtkiewicz J. Zinc Transporter 3 (ZnT3) in the Enteric Nervous System of the Porcine Ileum in Physiological Conditions and during Experimental Inflammation. Int J Mol Sci. 2017; 18(2).
  19. Gonkowski S, Burlinski P, Calka J. Proliferative enteropathy (PE): Induced changes in galanin-like immunoreactivity in the enteric nervous system of the porcine distal colon. Acta Veterinaria. 2009; 59(4): 321–330.
  20. Guo J, Zhao MH, Shin KT, et al. The possible molecular mechanisms of bisphenol A action on porcine early embryonic development. Sci Rep. 2017; 7(1): 8632.
  21. Hammack SE, May V. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies. Biol Psychiatry. 2015; 78(3): 167–177.
  22. Hashimoto H. [Psychiatric implications of PACAP signaling pathway]. Nihon Shinkei Seishin Yakurigaku Zasshi. 2012; 32(3): 133–137.
  23. Hökfelt T, Kellerth JO, Nilsson G, et al. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 1975; 100(2): 235–252.
  24. Itoh K, Yaoi T, Fushiki S. Bisphenol A, an endocrine-disrupting chemical, and brain development. Neuropathology. 2012; 32(4): 447–457.
  25. Jensen KJ, Alpini G, Glaser S. Hepatic nervous system and neurobiology of the liver. Compr Physiol. 2013; 3(2): 655–665.
  26. Kinch CD, Ibhazehiebo K, Jeong JH, et al. Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish. Proc Natl Acad Sci U S A. 2015; 112(5): 1475–1480.
  27. Kitraki E, Nalvarte I, Alavian-Ghavanini A, et al. Effects of pre- and post-natal exposure to bisphenol A on the stress system. Endocrine Disruptors. 2016; 4(1): e1184775.
  28. Kolšek K, Mavri J, Sollner Dolenc M. Reactivity of bisphenol A-3,4-quinone with DNA. A quantum chemical study. Toxicol In Vitro. 2012; 26(1): 102–106.
  29. Kozłowska A, Wojtkiewicz J, Majewski M, et al. Localization of substance P, calcitonin gene related peptide and galanin in the nerve fibers of porcine cystic ovaries. Folia Histochem Cytobiol. 2011; 49(4): 622–630.
  30. Lasaga M, Debeljuk L. Tachykinins and the hypothalamo-pituitary-gonadal axis: An update. Peptides. 2011; 32(9): 1972–1978.
  31. Lautt WW. Hepatic nerves: a review of their functions and effects. Can J Physiol Pharmacol. 1980; 58(2): 105–123.
  32. Lautt WW. Hepatic circulation: Physiology and pathophysiology. In Colloquium Series on Integrated Systems: Physiology: from Molecule to Function. Morgan & Claypool Life Sciences: San Rafael, CA, USA. 2009; book 1. : 83–119.
  33. Lian J, De Santis M, He M, et al. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways. Pharmacol Res. 2015; 95-96: 20–26.
  34. Litten-Brown JC, Corson AM, Clarke L. Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview. Animal. 2010; 4(6): 899–920.
  35. Majewski M, Bossowska A, Gonkowski S, et al. Neither axotomy nor target-tissue inflammation changes the NOS- or VIP-synthesis rate in distal bowel-projecting neurons of the porcine inferior mesenteric ganglion (IMG). Folia Histochem Cytobiol. 2002; 40(2): 151–152.
  36. Makowska K, Obremski K, Zielonka L, et al. The influence of low doses of zearalenone and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI) neurons in the ENS of the porcine descending colon. Toxins (Basel). 2017; 9(3).
  37. McCulloch J, Uddman R, Kingman TA, et al. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci U S A. 1986; 83(15): 5731–5735.
  38. Meisner H, Carter JR. Regulation of lipolysis in adipose tissue. Horiz Biochem Biophys. 1977; 4: 91–129.
  39. Mizuno Y, Kondo K, Terashima Y, et al. Anorectic effect of pituitary adenylate cyclase activating polypeptide (PACAP) in rats: lack of evidence for involvement of hypothalamic neuropeptide gene expression. J Neuroendocrinol. 1998; 10(8): 611–616.
  40. Morley JE, Horowitz M, Morley PM, et al. Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice. Peptides. 1992; 13(6): 1133–1135.
  41. Mueller K, Sacher J, Arelin K, et al. Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study. Transl Psychiatry. 2012; 2: e200.
  42. O'Connor TM, O'Connell J, O'Brien DI, et al. The role of substance P in inflammatory disease. J Cell Physiol. 2004; 201(2): 167–180.
  43. Palus K, Rytel L. Co-localisation of cocaine- and amphetamine-regulated transcript peptide and vasoactive intestinal polypeptide in the myenteric plexus of the porcine transverse colon. Folia Morphol. 2013; 72(4): 328–332.
  44. Michaela P, Mária K, Silvia H, et al. Bisphenol A differently inhibits CaV3.1, CaV3.2 and CaV3.3 calcium channels. Arch Exp Pathol Pharmakol. 2013; 387(2): 153–163.
  45. Rachoń D. Endocrine disrupting chemicals (EDCs) and female cancer: Informing the patients. Rev Endocr Metab Disord. 2015; 16(4): 359–364.
  46. Reif DM, Martin MT, Tan SW, et al. Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect. 2010; 118(12): 1714–1720.
  47. Rękawek W, Sobiech P, Gonkowski S, et al. Distribution and chemical coding patterns of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) neurons in the enteric nervous system of the porcine stomach cardia. Pol J Vet Sci. 2015; 18(3): 515–522.
  48. Jovanovic T, Norrholm SD, Davis J, et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011; 470(7335): 492–497.
  49. Sandoval-Alzate HF, Agudelo-Zapata Y, González-Clavijo AM, et al. Serum galanin levels in young healthy lean and obese non-diabetic men during an oral glucose tolerance test. Sci Rep. 2016; 6: 31661.
  50. Schwarz MJ, Ackenheil M. The role of substance P in depression: therapeutic implications. Dialogues Clin Neurosci. 2002; 4(1): 21–29.
  51. Simoneau C, Valzacchi S, Morkunas V, et al. Comparison of migration from polyethersulphone and polycarbonate baby bottles. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011; 28(12): 1763–1768.
  52. Surendran S, Kondapaka SB. Altered expression of neuronal nitric oxide synthase in the duodenum longitudinal muscle-myenteric plexus of obesity induced diabetes mouse: implications on enteric neurodegeneration. Biochem Biophys Res Commun. 2005; 338(2): 919–922.
  53. Taborsky GJ, Dunning BE, Havel PJ, et al. The canine sympathetic neuropeptide galanin: a neurotransmitter in pancreas, a neuromodulator in liver. Horm Metab Res. 1999; 31(5): 351–354.
  54. Trasande L, Attina TM, Blustein J. Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA. 2012; 308(11): 1113–1121.
  55. Vandenberg L, Ehrlich S, Belcher S, et al. Low dose effects of bisphenol A. Endocrine Disruptors. 2014; 1(1): e26490.
  56. Verma N, Rettenmeier AW, Schmitz-Spanke S. Recent advances in the use of Sus scrofa (pig) as a model system for proteomic studies. Proteomics. 2011; 11(4): 776–793.
  57. Wang Hx, Zhou Y, Tang Cx, et al. Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study. Environ Health. 2012; 11: 79.
  58. Wojtkiewicz J, Gonkowski S, Bladowski M, et al. Characterisation of cocaine- and amphetamine- regulated transcript-like immunoreactive (CART-LI) enteric neurons in the porcine small intestine. Acta Vet Hung. 2012; 60(3): 371–381.
  59. Wojtkiewicz J, Makowska K, Bejer-Olenska E, et al. Zinc transporter 3 (Znt3) as an active substance in the enteric nervous system of the porcine esophagus. J Mol Neurosci. 2017; 61(3): 315–324.
  60. Wojtkiewicz J, Rytel L, Makowska K, et al. Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or neuromodulators in the enteric nervous system of the porcine esophagus. Biometals. 2017; 30(3): 393–403.
  61. Zalko D, Soto AM, Canlet C, et al. Bisphenol a exposure disrupts neurotransmitters through modulation of transaminase activity in the brain of rodents. Endocrinology. 2016; 157(5): 1736–1739.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.: +48 58 320 94 94, faks: +48 58 320 94 60, e-mail: viamedica@viamedica.pl