1. bookVolume 21 (2021): Issue 4 (October 2021)
Journal Details
License
Format
Journal
First Published
25 Nov 2011
Publication timeframe
4 times per year
Languages
English
access type Open Access

Effect of Chemically-Induced Diabetes Mellitus on Phenotypic Variability of the Enteric Neurons in the Descending Colon in the Pig

Published Online: 28 Oct 2021
Page range: 1403 - 1422
Received: 12 Jul 2020
Accepted: 01 Dec 2020
Journal Details
License
Format
Journal
First Published
25 Nov 2011
Publication timeframe
4 times per year
Languages
English
Abstract

Gastrointestinal neuropathy in diabetes is one of numerous diseases resulting in abnormal functioning of the gastrointestinal tract (GIT), and it may affect any section of the GIT, including the descending colon. In the gastrointestinal system, the neurons are arranged in an interconnecting network defined as the enteric nervous system (ENS) which includes the myenteric plexus and the submucosal plexuses: inner and outer. Regular functioning of the ENS is determined by normal synthesis of the neurotransmitters and neuromodulators. This paper demonstrates the effect of hyperglycaemia on the number of enteric neurons which are immunoreactive to: neural isoform of nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), galanin (GAL), calcitonin generelated peptide (CGRP) and cocaine amphetamine-regulated transcript (CART) in the porcine descending colon. It was demonstrated that there was a statistically significant increase in the number of neurons within the myenteric plexus immunoreactive to all investigated substances. In the outer submucosal plexus, the CART-positive neurons were the only ones not to change, whereas no changes were recorded for nNOS or CART in the inner submucosal plexus. This study is the first study to discuss quantitative changes in the neurons immunoreactive to nNOS, VIP, GAL, CGRP and CART in the descending colon in diabetic pigs.

Keywords

Arciszewski M. B., Ekblad E. (2005). Effects of vasoactive intestinal peptide and galanin on survival of cultured porcine myenteric neurons. Regul. Pept., 125: 185–192.Search in Google Scholar

Barada K. A., Saadé N. E., Atweh S. F., Khoury C. I., Nassar C. F. (2000). Calcitonin generelated peptide regulates amino acid absorption across rat jejunum. Regul. Pept., 90: 39–45.Search in Google Scholar

Barbiers M., Timmermans J. P., Scheuermann D. W., Adriaensen D., Mayer B., De Groodt Lasseel M. H. A. (1994). Nitric oxide synthase-containing neurons in the pig large intestine: Topography, morphology, and viscerofugal projections. Microsc. Res. Tech., 29: 72–78.Search in Google Scholar

Belai A., Burnstock G. (1990). Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum. Gastroenterology, 98: 1427–1436.Search in Google Scholar

Belai A., Lincoln J., Milner P., Crowe R., Loesch A., Burnstock G. (1985). Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P. Gastroenterology, 89: 967–976.Search in Google Scholar

Belai A., Calcutt N. A., Carrington A. L., Diemel L. T., Tomlinson D. R., Burnstock G. (1996). Enteric neuropeptides in streptozotocindiabetic rats; effects of insulin and aldose reductase inhibition. Auton. Nerv. Syst., 58: 163–169.Search in Google Scholar

Botella A., Delvaux M., Frexinos J., Bueno L. (1992). Comparative effects of galanin on isolated smooth muscle cells from ileum in five mammalian species. Life. Sci., 50: 1253–1261.Search in Google Scholar

Brehmer A., Schrodl F., Neuhuber W. (2006). Morphology of VIP/nNOS-immunoreactive myenteric neurons in the human gut. Histochem. Cell. Biol., 125: 557–565.Search in Google Scholar

Brehmer A., Rupprecht H., Neuhuber W. (2010). Two submucosal nerve plexus in human intestines. Histochem. Cell. Biol. 133: 149–161.Search in Google Scholar

Brenneman D. E., Hill J. M., Glazner G. W., Gozes I., Philips T. M. (1995). Interleukin-1α and vasoactive intestinal peptide: enigmatic regulation of neuronal survival. Int. J. Dev. Neurosci., 13: 187–200.Search in Google Scholar

Brenneman D. E., Philips T. M., Hauser J., Hill J. M., Spong C., Gozes I. (2003). Complex array of cytokines released by vasoactive intestinal peptide. Neuropeptides, 37: 111–119.Search in Google Scholar

Bulc M., Gonkowski S., Całka J. (2015). 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., 57: 376–385.Search in Google Scholar

Bulc M., Palus K., Zielonka L., Gajecka M., Całka J. (2017), Changes in expression of inhibitory substances in the intramural neurons of the stomach following streptozotocin- induced diabetes in the pig. World. J. Gastroenterol., 23: 6088–6099.Search in Google Scholar

Bulc M., Palus K., Całka J., Zielonka L. (2018). Changes in immunoreactivity of sensory substances within the enteric nervous system of the porcine stomach during experimentally induced diabetes. J. Diabetes. Res., 2018: 1–18.Search in Google Scholar

Bulc M., Palus K., Dąbrowski M., Całka J. (2019). Hyperglycaemia-induced downregulation in expression of nNOS intramural neurons of the small intestine in the pig. Int. J. Mol. Sci., 20: 1681.Search in Google Scholar

Burleigh D. E., Banks M. R. (2007). Stimulation of intestinal secretion by vasoactive intestinal peptide and cholera toxin. Auton. Neurosci. Bas. Clin., 133: 64–75.Search in Google Scholar

Chandrasekharan B., Srinivasan S. (2007). Diabetes and the enteric nervous system. Neurogastroenterol. Motil., 19: 951–960.Search in Google Scholar

Clerc N., Furness J. B. (2004). Intrinsic primary afferent neurones of the digestive tract. Neurogastroenterol. Motil., 16: 24–27.Search in Google Scholar

Costa M., Furness J. B. (1982). Neuronal peptides in the intestine. Br. Med. Bull., 38: 247–252.Search in Google Scholar

Demedts I., Masaoka T., Kindt S., De Hertogh G., Geboes K., Farré R., Vanden Berghe P., Tack J. (2013). Gastrointestinal motility changes and myenteric plexus alterations in spontaneously diabetic biobreeding rats. J. Neurogastroenterol. Motil., 19: 161–170.Search in Google Scholar

Ekblad E. (2006). CART in the enteric nervous system. Peptides, 27: 2024–2030.Search in Google Scholar

Ekblad E., Kuhar M., Wierup N., Sundler F. (2003). Cocaine- and amphetamine-regulated transcript: distribution and function in rat gastrointestinal tract. Neurogastroenterol. Motil., 15: 545–557.Search in Google Scholar

Ellis L. M., Mawe G.M., (2003). Distribution and chemical coding of cocaine- and amphetamineregulated transcript peptide (CART)-immunoreactive neurons in the guinea pig bowel. Cell. Tissue. Res., 312: 265–274.Search in Google Scholar

Evangelista S., Tramontana M. (1993). Involvement of calcitonin gene-related peptide in rat experimental colitis. J. Physiol., 87: 277–280.Search in Google Scholar

Feher E., Batbayar B., Ver A. (2006). Changes of the different neuropeptide-containing nerve fibres and immune cells in the diabetic rat’s alimentary tract. Ann. N.Y. Acad. Sci., 1084: 280–295.Search in Google Scholar

Foxt-Threlkeld J. E. T., Mc Donald T. J., Cipris S., Woskowska Z., Daniel E. E. (1991). Galanin inhibition of vasoactive intestinal polypeptide release and circular muscle motility in the isolated perfused canine ileum. Gastroenterology, 101: 1471–1476.Search in Google Scholar

Furness J. B. (2000). Types of neurons in the enteric nervous system. J. Auton. Nerv. Syst., 81: 87–96.Search in Google Scholar

Furness J. B. (2006). The organisation of the autonomic nervous system: peripheral connections. Auton. Neurosci., 130: 1–5.Search in Google Scholar

Furness J. B. (2012). The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroent. Hepatol., 5: 286–294.Search in Google Scholar

Furness J. B., Callaghan B. P., Rivera L. R., Cho H. J. (2014). The enteric nervous system and gastrointestinal innervation: Integrated local and central control. Adv. Exp. Med. Biol., 817: 39–71.Search in Google Scholar

Gatopoulou A. N., Papanas E., Maltezos A. (2012). Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice. Eur. J. Intern. Med., 6: 499–505.Search in Google Scholar

Gonkowski S., Rytel L. (2019). Somatostatin as an active substance in the mammalian enteric nervous system. Int. J. Mol. Sci., 20: 4461.Search in Google Scholar

Gonkowski S., Burliński P., Skobowiat C., Majewski M., Arciszewski M. B., Radziszewski P., Całka J. (2009). Distribution of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) nerve structures in the porcine large intestine. Acta. Vet. Hung., 4: 509–520.Search in Google Scholar

Gonkowski S., Burliński P., Skobowiat C., Majewski M., Całka J. (2010). Inflammation-and axotomy-induced changes in galanin-like immunoreactive (GAL-LI) nerve structures in the porcine descending colon. Acta. Vet. Hung., 58: 91–103.Search in Google Scholar

Greenwood-Van Meerveld B., Johnson A. C., Grundy D. (2017). Gastrointestinal physiology and function. Handb. Exp. Pharmacol., 239: 1–16.Search in Google Scholar

Grüssner R., Nakhleh R., Grüssner A., Tomadze G., Diem P., Sutherland D. (1993). Streptozotocin-induced diabetes mellitus in pigs. Horm. Metab. Res., 25: 199–203.Search in Google Scholar

Jaworski J. N., Jones D. C. (2006). The role of CART in the reward/reinforcing properties of psychostimulants. Peptides, 27: 1993–2004.Search in Google Scholar

Juranek J. K., Aleshin A., Rattigan E. M. (2010). Morphological changes and immunohistochemical expression of RAGE and its ligands in the sciatic nerve of hyperglycemic pig (Sus scrofa). Biochem. Insights., 2010: 47–59.Search in Google Scholar

Kaiser E. A., Rea B. J., Kuburas A., Kovacevich B. R., Garcia-Martinez L. F., Recober A., Russo A. F. (2017). Anti-CGRP antibodies block CGRP-induced diarrhea in mice. Neuropeptides, 64: 95–99.Search in Google Scholar

Kaleczyc J., Klimczuk M., Franke-Radowiecka A., Sienkiewicz W., Majewski M., Łakomy M. (2007). 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., 36: 186–193.Search in Google Scholar

Keast J. R., Furness J. B., Costa M. (1985). Distribution of certain peptide-containing nerve fibres and endocrine cells in the gastrointestinal mucosa in five mammalian species. J. Comp. Neurol., 236: 403–422.Search in Google Scholar

Lambrecht N., Burchert M., Respondek M., Müller K. M., Peskar B. M. (1993). Role of calcitonin gene-related peptide and nitric oxide in the gastroprotective effect of capsaicin in the rat. Gastroenterology, 104: 1371–1380.Search in Google Scholar

Li F. J., Zou Y. Y., Cui Y., Yin Y., Guo G., Lu F. G. (2013). Calcitonin gene-related peptide is a promising marker in ulcerative colitis. Dig. Dis. Sci., 58: 686–693.Search in Google Scholar

Makowska K. (2018). Chemically induced inflammation and nerve damage affect the distribution of vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nervous structures in the descending colon of the domestic pig. Neurogastroenterol. Motil., 30: 13439.Search in Google Scholar

Makowska K., Gonkowski S. (2018). 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., 19: 548.Search in Google Scholar

Makowska K., Gonkowski S. (2019). Age and sex-dependent differences in the neurochemical characterization of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nervous structures in the porcine descending colon. Int. J. Mol. Sci., 20: 1024.Search in Google Scholar

Makowska K., Gonkowski S., Zielonka L., Dabrowski M., Calka J. (2017). T2 toxininduced 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., 31: 136–147.Search in Google Scholar

Nassar C. F., Abdallah L. E., Barada K. A., Atweh S. F., Saadé N. F. (1995). Effects of intravenous vasoactive intestinal peptide injection on jejunal alanine absorption and gastric acid secretion in rats. Regul. Pept., 55: 261–267.Search in Google Scholar

Nuki C., Kawasaki H., Kitamura K., Takenaga M., Kangawa K., Eto T. (1993). Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. Biochem. Biophys. Res. Commun., 196: 245–251.Search in Google Scholar

Ohno T., Hattori Y., Komine R., Ae T., Mizuguchi S., Arai K., Saeki T., Suzuki T., Hosono K., Hayashi I. (2008). Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis. Gastroenterology, 134: 215–225.Search in Google Scholar

Palus K., Bulc M., Całka J. (2018 a). 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, 69: 47–59.Search in Google Scholar

Palus K., Makowska K., Całka J. (2018 b). Acrylamide-induced alterations in the cocaine- and amphetamine-regulated peptide transcript (CART)-like immunoreactivity within the enteric nervous system of the porcine small intestines. Ann. Anat., 219: 94–101.Search in Google Scholar

Palus K., Makowska K., Całka J. (2019). Alterations in galanin-like immunoreactivity in the enteric nervous system of the porcine stomach following acrylamide supplementation. Int. J. Mol. Sci., 20: 3345.Search in Google Scholar

Philips R. J., Powley T. L. (2007). Innervation of the gastrointestinal tract: Patterns of aging. Auton. Neurosci., 136: 1–19.Search in Google Scholar

Rees D. A., Alcolado J. C. (2005). Animal models of diabetes mellitus. Diabet. Med., 22: 359–370.Search in Google Scholar

Sanders K. M., Ward S. M. (1992). Nitric oxide as a mediator of nonadrenergic, noncholinergic neurotransmission. Am. J. Physiol., 262: G379–G392.Search in Google Scholar

Schleiffer R., Raul F. (1997). Nitric oxide and the digestive system in mammals and nonmammalian vertebrates. Comp. Biochem. Physiol., 118A: 965–974.Search in Google Scholar

Shah V., Lyford G., Gores G., Farrugia G. (2004). Nitric oxide in gastrointestinal health and disease. Gastroenterology, 126: 903–913.Search in Google Scholar

Skobowiat C., Calka J., Majewski M. (2011). Axotomy induced changes in neuronal plasticity of sympathetic chain ganglia (SChG) neurons supplying descending colon in the pig. Exp. Mol. Pathol., 90: 13–18.Search in Google Scholar

Swindle M. M. (2012). The development of swine models in drug discovery and development. Future. Med. Chem., 4: 1771–1772.Search in Google Scholar

Swindle M. M., Smith A. C. (1998). Comparative anatomy and physiology of the pig. Scand. J. Lab. Anim. Sci., 25: 11–21.Search in Google Scholar

Szymanska K., Calka J., Gonkowski S. (2018). Nitric oxide as an active substance in the enteric neurons of the porcine digestive tract in physiological conditions and under intoxication with bisphenol A (BPA). Nitric. Oxide, 80: 1–11.Search in Google Scholar

Timmermans J. P., Scheuermann D. W., Stach W., Adriaensen D., de Groodt-Lesseal M. H. A. (1992 a). Functional morphology of the enteric nervous system with special reference to large mammals. Eur. J. Morphol., 30: 113–122.Search in Google Scholar

Timmermans J. P., Scheuermann D. W., Barbiers M., Adriaensen D., Stach W., Van Hee R., De Groodt-Lasseel M. H. A. (1992 b). Calcitonin gene-related peptide-like immunoreactivity in the human small intestine. Acta. Anat., 143: 48–53.Search in Google Scholar

Vasina V., Barbara G., Talamonti L. (2006). Enteric neuroplasticity evoked by inflammation. Auton. Neurosci., 127: 264–272.Search in Google Scholar

Vincent A. M., Russell J. W., Low P., Feldman E. L. (2004). Oxidative stress in the pathogenesis of diabetic neuropathy. Endocrin. Rev., 25: 612–628.Search in Google Scholar

Vinik A. I., Maser R. E., Mitchell B. D., Freeman R. (2003). Diabetic autonomic neuropathy Diabetes. Care, 5: 1553–1579.Search in Google Scholar

Whittaker V. P. (1989). Vasoactive intestinal polypeptide (VIP) as a cholinergic co-transmitter: some recent results. Cell. Biol. Int. Rep., 13: 1039–1051.Search in Google Scholar

Wolf M., Schrödl F., Neuhuber W., Brehmer A. (2007). Calcitonin gene-related peptide: A marker for putative primary afferent neurons in the pig small intestinal myenteric plexus? Anat. Rec., 290: 1273–1279.Search in Google Scholar

Yarandi S. S., Srinivasan S. (2014). Diabetic gastrointestinal motility disorders and the role of enteric nervous system: Current status and future directions. Neurogastroenterol. Motil., 26: 611–624.Search in Google Scholar

Young H. M., Furness J. B., Shuttleworth C. W. R., Bredt D. S., Snyder S. H. (1992). Colocalization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry, 97: 375–378.Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo