View More View Less
  • 1 University of Szeged Department of Physiology, Anatomy and Neuroscience Szeged Hungary
Restricted access

Nitrergic myenteric neurons are especially susceptible to the development of neuropathy in functional gastrointestinal disorders. Investigations of the similarities and dissimilarities in the organization of nitrergic neurons in the various mammalian species are therefore important in an effort to determine the extent to which the results obtained in different animal models can be generalized. In the present work, the density and the spatial organization of the nitrergic neurons in the myenteric plexus of the duodenum were investigated in 7 mammalian species. After nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, the Plexus Pattern Analysis software (PPAs) was applied to count the nuclei of nitrergic neurons, calculate the proportions of the areas covered by the plexus and perform randomization analysis. All 7 species exhibited a large population of nitrergic myenteric neurons, with densities in the range 12–56 cells/mm 2 . The distribution patterns of these neurons differed markedly in the different species, however, the rat was the only species in which the nitrergic neurons appeared to be randomly distributed. The PPAs in conjunction with NADPH-d histochemistry proved to be a simple and fast tool with which to reveal similarities and dissimilarities in the spatial arrangement of the nitrergic neurons in the different species.

  • Balaskas, C., Saffrey, M. J., Burnstock, G. (1995) Distribution of NADPH-diaphorase activity in the embryonic chicken gut. Anat. Embryol. (Berl) 192 , 239–245.

    Burnstock G. , 'Distribution of NADPH-diaphorase activity in the embryonic chicken gut ' (1995 ) 192 Anat. Embryol. (Berl) : 239 -245.

    • Search Google Scholar
  • Belai, A., Cooper, S., Burnstock, G. (1995) Effect of age on NADPH-diaphorase-containing myenteric neurons of rat ileum and proximal colon. Cell Tissue Res. 279 , 379–383.

    Burnstock G. , 'Effect of age on NADPH-diaphorase-containing myenteric neurons of rat ileum and proximal colon ' (1995 ) 279 Cell Tissue Res. : 379 -383.

    • Search Google Scholar
  • Belai, A., Schmidt, H. H., Hoyle, C. H., Hassall, C. J., Saffrey, M. J., Moss, J., Förstermann, U., Murad, F., Burnstock, G. (1992) Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut. Neurosci. Lett. 143 , 60–64.

    Burnstock G. , 'Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut ' (1992 ) 143 Neurosci. Lett. : 60 -64.

    • Search Google Scholar
  • Boeckxstaens, G. E., Pelckmans, P. A., Ruytjens, I. F., Bult, H., DeMan, J. G., Herman, A. G., Van Maercke, Y. M. (1991) Bioassay of nitric oxide released upon stimulation of non-adrenergic noncholinergic nerves in the canine ileocolonic junction. Br. J. Pharmacol. 103 , 1085–1091.

    Maercke Y. M. , 'Bioassay of nitric oxide released upon stimulation of non-adrenergic noncholinergic nerves in the canine ileocolonic junction ' (1991 ) 103 Br. J. Pharmacol. : 1085 -1091.

    • Search Google Scholar
  • Bosman, C., Devito, R., Fusilli, S., Boldrini, R. (2001) A new hypothesis on the pathogenesis of intestinal pseudo-obstruction by intestinal neuronal dysplasia (IND). Pathol. Res. Pract. 197 , 789–796.

    Boldrini R. , 'A new hypothesis on the pathogenesis of intestinal pseudo-obstruction by intestinal neuronal dysplasia (IND) ' (2001 ) 197 Pathol. Res. Pract. : 789 -796.

    • Search Google Scholar
  • Bult, H., Boeckxstaens, G. E., Pelckmans, P. A., Jordaens, F. H., Van Maercke, Y. M., Herman, A. G. (1990) Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345 , 346–347.

    Herman A. G. , 'Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter ' (1990 ) 345 Nature : 346 -347.

    • Search Google Scholar
  • Cellek, S., Qu, W., Schmidt, A. M., Moncada, S. (2004) Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: a new insight into selective nitrergic neuropathy in diabetes. Diabetologia 47 , 331–339.

    Moncada S. , 'Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: a new insight into selective nitrergic neuropathy in diabetes ' (2004 ) 47 Diabetologia : 331 -339.

    • Search Google Scholar
  • Chaudhury, A., Shariff, A., Srinivas, M., Sabherwal, U. (2004) Changes in nitrergic innervation of defunctionalized rat colon after diversion colostomy. Neurogastroenterol. Motil. 16 , 475–487.

    Sabherwal U. , 'Changes in nitrergic innervation of defunctionalized rat colon after diversion colostomy ' (2004 ) 16 Neurogastroenterol. Motil. : 475 -487.

    • Search Google Scholar
  • Cracco, C., Filogamo, G. (1994) Quantitative study of the NADPH-diaphorase-positive myenteric neurons of the rat ileum. Neuroscience 61 , 351–359.

    Filogamo G. , 'Quantitative study of the NADPH-diaphorase-positive myenteric neurons of the rat ileum ' (1994 ) 61 Neuroscience : 351 -359.

    • Search Google Scholar
  • Cserni, T., Paran, S., Puri, P. (2007) The effect of age on colocalization of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining in enteric neurons in an experimental model. J. Pediatr. Surg. 42 , 300–304.

    Puri P. , 'The effect of age on colocalization of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining in enteric neurons in an experimental model ' (2007 ) 42 J. Pediatr. Surg. : 300 -304.

    • Search Google Scholar
  • De Giorgio, R., Parodi, J. E., Brecha, N. C., Brunicardi, F. C., Becker, J. M., Go, V. L., Sternini, C. (1994) Nitric oxide producing neurons in the monkey and human digestive system. J. Comp. Neurol. 342 , 619–627.

    Sternini C. , 'Nitric oxide producing neurons in the monkey and human digestive system ' (1994 ) 342 J. Comp. Neurol. : 619 -627.

    • Search Google Scholar
  • Furness, J. B., Li, Z. S., Young, H. M., Förstermann, U. (1994) Nitric oxide synthase in the enteric nervous system of the guinea-pig: a quantitative description. Cell Tissue Res. 277 , 139–149.

    Förstermann U. , 'Nitric oxide synthase in the enteric nervous system of the guinea-pig: a quantitative description ' (1994 ) 277 Cell Tissue Res. : 139 -149.

    • Search Google Scholar
  • Gábriel, R., Pásztor, I., Dénes, V., Wilhelm, M. (1998) Some neurohistochemical properties of nerve elements in myenteric plexus of rabbit ileum: similarities and dissimilarities to the rodent pattern. Cell Tissue Res. 292 , 283–291.

    Wilhelm M. , 'Some neurohistochemical properties of nerve elements in myenteric plexus of rabbit ileum: similarities and dissimilarities to the rodent pattern ' (1998 ) 292 Cell Tissue Res. : 283 -291.

    • Search Google Scholar
  • Hope, B. T., Michael, G. J., Knigge, K. M., Vincent, S. R. (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc. Natl. Acad. Sci. USA. 88 , 2811–2814.

    Vincent S. R. , 'Neuronal NADPH diaphorase is a nitric oxide synthase ' (1991 ) 88 Proc. Natl. Acad. Sci. USA. : 2811 -2814.

    • Search Google Scholar
  • Izbéki, F., Wittman, T., Rosztóczy, A., Linke, N., Bódi, N., Fekete, E., Bagyánszki, M. (2008) Immediate insulin treatment prevents gut motility alterations and loss of nitrergic neurons in the ileum and colon of rats with streptozotocin-induced diabetes. Diabetes. Res. Clin. Pract. 80 , 192–198.

    Bagyánszki M. , 'Immediate insulin treatment prevents gut motility alterations and loss of nitrergic neurons in the ileum and colon of rats with streptozotocin-induced diabetes ' (2008 ) 80 Diabetes. Res. Clin. Pract. : 192 -198.

    • Search Google Scholar
  • Jarvinen, M. K., Wollmann, W. J., Powrozek, T. A., Schultz, J. A., Powley, T. L. (1999) Nitric oxide synthase-containing neurons in the myenteric plexus of the rat gastrointestinal tract: distribution and regional density. Anat. Embryol. (Berl). 199 , 99–112.

    Powley T. L. , 'Nitric oxide synthase-containing neurons in the myenteric plexus of the rat gastrointestinal tract: distribution and regional density ' (1999 ) 199 Anat. Embryol. (Berl). : 99 -112.

    • Search Google Scholar
  • Karaosmanoglu, T., Aygun, B., Wade, P. R., Gershon, M. D. (1996) Regional differences in the number of neurons in the myenteric plexus of the guinea pig small intestine and colon: an evaluation of markers used to count neurons. Anat. Rec. 244 , 470–480.

    Gershon M. D. , 'Regional differences in the number of neurons in the myenteric plexus of the guinea pig small intestine and colon: an evaluation of markers used to count neurons ' (1996 ) 244 Anat. Rec. : 470 -480.

    • Search Google Scholar
  • Krecsmarik, M., Izbéki, F., Bagyánszki, M., Linke, N., Bódi, N., Kaszaki, J., Katarova, Z., Szabó, A., Fekete, E., Wittmann, T. (2006) Chronic ethanol exposure impairs neuronal nitric oxide synthase in the rat intestine. Alcohol. Clin. Exp. Res. 30 , 967–973.

    Wittmann T. , 'Chronic ethanol exposure impairs neuronal nitric oxide synthase in the rat intestine ' (2006 ) 30 Alcohol. Clin. Exp. Res. : 967 -973.

    • Search Google Scholar
  • Lefebvre, R. A., Barthó, L. (1997) Mechanism of nitric oxide-induced contraction in the rat isolated small intestine. Br. J. Pharmacol. 120 , 975–981.

    Barthó L. , 'Mechanism of nitric oxide-induced contraction in the rat isolated small intestine ' (1997 ) 120 Br. J. Pharmacol. : 975 -981.

    • Search Google Scholar
  • Lefebvre, R. A. (1995) Nitric oxide in the peripheral nervous system. Ann. Med. 27 , 379–388.

    Lefebvre R. A. , 'Nitric oxide in the peripheral nervous system ' (1995 ) 27 Ann. Med. : 379 -388.

    • Search Google Scholar
  • Mizuta, Y., Takahashi, T., Owyang, C. (1999) Nitrergic regulation of colonic transit in rats. Am. J. Physiol. 277 , G275–279.

    Owyang C. , 'Nitrergic regulation of colonic transit in rats ' (1999 ) 277 Am. J. Physiol. : G275 -279.

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

    Powley T. L. , 'Innervation of the gastrointestinal tract: patterns of aging ' (2007 ) 136 Auton. Neurosci. : 1 -19.

    • Search Google Scholar
  • Porter, A. J., Wattchow, D. A., Brookes, S. J., Costa, M. (2002) Cholinergic and nitrergic interneurons in the myenteric plexus of the human colon. Gut 51 , 70–75.

    Costa M. , 'Cholinergic and nitrergic interneurons in the myenteric plexus of the human colon ' (2002 ) 51 Gut : 70 -75.

    • Search Google Scholar
  • Román, V., Bagyánszki, M., Krecsmarik, M., Horváth, A., Resch, B. A., Fekete, E. (2004) Spatial pattern analysis of nitrergic neurons in the developing myenteric plexus of the human fetal intestine. Cytometry A .57, 108–112.

    Fekete E. , 'Spatial pattern analysis of nitrergic neurons in the developing myenteric plexus of the human fetal intestine ' (2004 ) 57 Cytometry A. : 108 -112.

    • Search Google Scholar
  • Scherer-Singler, U., Vincent, S. R., Kimura, H., McGeer, E. G. (1983) Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry. J. Neurosci. Methods 9 , 229–234.

    McGeer E. G. , 'Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry ' (1983 ) 9 J. Neurosci. Methods : 229 -234.

    • Search Google Scholar
  • Spångéus, A., Suhr, O., El-Salhy, M. (2000) Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes. Histol. Histopathol. 15 , 739–744.

    El-Salhy M. , 'Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes ' (2000 ) 15 Histol. Histopathol. : 739 -744.

    • Search Google Scholar
  • Takaki, M., Wood, J. D., Gershon, M. D. (1985) Heterogeneity of ganglia of the guinea pig myenteric plexus: an in vitro study of the origin of terminals within single ganglia using a covalently bound fluorescent retrograde tracer. J. Comp. Neurol. 235 , 488–502.

    Gershon M. D. , 'Heterogeneity of ganglia of the guinea pig myenteric plexus: an in vitro study of the origin of terminals within single ganglia using a covalently bound fluorescent retrograde tracer ' (1985 ) 235 J. Comp. Neurol. : 488 -502.

    • Search Google Scholar
  • Teramoto, M., Domoto, T., Tanigawa, K., Yasui, Y., Tamura, K. (1996) Distribution of nitric oxide synthase-containing nerves in the aganglionic intestine of mutant rats: a histochemical study. J. Gastroenterol. 31 , 214–223.

    Tamura K. , 'Distribution of nitric oxide synthase-containing nerves in the aganglionic intestine of mutant rats: a histochemical study ' (1996 ) 31 J. Gastroenterol. : 214 -223.

    • Search Google Scholar
  • Timmermans, J. P., Barbiers, M., Scheuermann, D. W., Bogers, J. J., Adriaensen, D., Fekete, E., Mayer, B., Van Marck, E. A., De Groodt-Lasseel, M. H. (1994) Nitric oxide synthase immunoreactivity in the enteric nervous system of the developing human digestive tract. Cell Tissue Res. 275 , 235–245.

    Groodt-Lasseel M. H. , 'Nitric oxide synthase immunoreactivity in the enteric nervous system of the developing human digestive tract ' (1994 ) 275 Cell Tissue Res. : 235 -245.

    • Search Google Scholar
  • Van Ginneken, C., Van Meir, F., Sommereyns, G., Sys, S., Weyns, A. (1998) Nitric oxide synthase expression in enteric neurons during development in the pig duodenum. Anat. Embryol. (Berl). 198 , 399–408.

    Weyns A. , 'Nitric oxide synthase expression in enteric neurons during development in the pig duodenum ' (1998 ) 198 Anat. Embryol. (Berl). : 399 -408.

    • Search Google Scholar
  • Van Ginneken, C., van Meir, F., Sys, S., Weyns, A. (2001) Stereologic description of the changing expression of constitutive nitric oxide synthase and heme oxygenase in the enteric plexuses of the pig small intestine during development. J. Comp. Neurol. 437 , 118–128.

    Weyns A. , 'Stereologic description of the changing expression of constitutive nitric oxide synthase and heme oxygenase in the enteric plexuses of the pig small intestine during development ' (2001 ) 437 J. Comp. Neurol. : 118 -128.

    • Search Google Scholar
  • Wang, Z. Q., Watanabe, Y., Toki, A., Kohno, S., Hasegawa, S., Hamazaki, M. (2000) Involvement of endogenous nitric oxide and c-kit-expressing cells in chronic intestinal pseudo-obstruction. J. Pediatr. Surg. 35 , 539–544.

    Hamazaki M. , 'Involvement of endogenous nitric oxide and c-kit-expressing cells in chronic intestinal pseudo-obstruction ' (2000 ) 35 J. Pediatr. Surg. : 539 -544.

    • Search Google Scholar
  • Wiley, J. W. (2002) Aging and neural control of the GI tract: III. Senescent enteric nervous system: lessons from extraintestinal sites and nonmammalian species. Am. J. Physiol. Gastrointest. Liver Physiol. 283 , G1020–1026.

    Wiley J. W. , 'Aging and neural control of the GI tract: III. Senescent enteric nervous system: lessons from extraintestinal sites and nonmammalian species ' (2002 ) 283 Am. J. Physiol. Gastrointest. Liver Physiol. : G1020 -1026.

    • Search Google Scholar
  • Wilhelm, M., Bátori, Z., Pásztor, I., Gábriel, R. (1998) NADPH-diaphorase positive myenteric neurons in the ileum of guinea-pig, rat, rabbit and cat: a comparative study. Eur. J. Morphol. 36 , 143–152.

    Gábriel R. , 'NADPH-diaphorase positive myenteric neurons in the ileum of guinea-pig, rat, rabbit and cat: a comparative study ' (1998 ) 36 Eur. J. Morphol. : 143 -152.

    • Search Google Scholar
  • Young, H. M., Furness, J. B., Sewell, P., Burcher, E. F., Kandiah, C. J. (1993) Total numbers of neurons in myenteric ganglia of the guinea-pig small intestine. Cell Tissue Res. 272 , 197–200.

    Kandiah C. J. , 'Total numbers of neurons in myenteric ganglia of the guinea-pig small intestine ' (1993 ) 272 Cell Tissue Res. : 197 -200.

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

    Snyder S. H. , 'Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guineapig intestine ' (1992 ) 97 Histochemistry : 375 -378.

    • Search Google Scholar