Skip to main content
Journal of Anatomy logoLink to Journal of Anatomy
. 1998 May;192(Pt 4):479–488. doi: 10.1046/j.1469-7580.1998.19240479.x

The effects of age on the overall population and on subpopulations of myenteric neurons in the rat small intestine

R J R JOHNSON 1 , M SCHEMANN 2 , R M SANTER 3 , T COWEN 1 ,
PMCID: PMC1467802  PMID: 9723975

Abstract

Previous studies on ageing animal and human subjects have demonstrated a significant overall decline in neuronal numbers in the myenteric plexus of the enteric nervous system (ENS). Our study aimed to confirm this observation by counting myenteric neurons stained with the panneuronal markers PGP 9.5 and NADH-diaphorase. We also wished to examine the possibility that particular subpopulations of neurons are vulnerable. Therefore, we have immunostained and counted a number of nerve cell groups within the myenteric plexus of old and young Sprague Dawley rats using markers which reflect some of the neuronal phenotypes present, including ChAT and VIP. The number of neurons demonstrating NADH-diaphorase activity was significantly reduced (P<0.05) by approximately 15% in old rats. However, the number of neurons stained for PGP 9.5 immunohistochemistry was not reduced and demonstrated larger numbers of neurons than the NADH-diaphorase method. None of the other neuronal markers studied showed any significant reductions with age. In contrast to previous work, this study has gathered little evidence for extensive cell loss in the myenteric plexus of the aged rat, either in overall populations, or in any of the principal functional groups of neurons.

Keywords: Enteric nervous system, myenteric plexus, ileum, ageing, cholinergic neurons, nitric oxide

Full Text

The Full Text of this article is available as a PDF (438.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker D. M., Watson S. P., Santer R. M. Evidence for a decrease in sympathetic control of intestinal function in the aged rat. Neurobiol Aging. 1991 Jul-Aug;12(4):363–365. doi: 10.1016/0197-4580(91)90023-d. [DOI] [PubMed] [Google Scholar]
  2. Belai A., Cooper S., Burnstock G. Effect of age on NADPH-diaphorase-containing myenteric neurones of rat ileum and proximal colon. Cell Tissue Res. 1995 Feb;279(2):379–383. doi: 10.1007/BF00318495. [DOI] [PubMed] [Google Scholar]
  3. Belai A., Schmidt H. H., Hoyle C. H., Hassall C. J., Saffrey M. J., Moss J., Förstermann U., Murad F., Burnstock G. Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut. Neurosci Lett. 1992 Aug 31;143(1-2):60–64. doi: 10.1016/0304-3940(92)90233-w. [DOI] [PubMed] [Google Scholar]
  4. Brookes S. J. Neuronal nitric oxide in the gut. J Gastroenterol Hepatol. 1993 Nov-Dec;8(6):590–603. doi: 10.1111/j.1440-1746.1993.tb01658.x. [DOI] [PubMed] [Google Scholar]
  5. Cowen T. Ageing in the autonomic nervous system: a result of nerve-target interactions? A review. Mech Ageing Dev. 1993 May;68(1-3):163–173. doi: 10.1016/0047-6374(93)90148-k. [DOI] [PubMed] [Google Scholar]
  6. Cowen T., Haven A. J., Burnstock G. Pontamine sky blue: a counterstain for background autofluorescence in fluorescence and immunofluorescence histochemistry. Histochemistry. 1985;82(3):205–208. doi: 10.1007/BF00501396. [DOI] [PubMed] [Google Scholar]
  7. Eaker E. Y., Sallustio J. E. The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine. Gastroenterology. 1994 Sep;107(3):666–674. doi: 10.1016/0016-5085(94)90113-9. [DOI] [PubMed] [Google Scholar]
  8. Fehér E., Pénzes L. Density of substance P, vasoactive intestinal polypeptide and somatostatin-containing nerve fibers in the ageing small intestine of the rats. Gerontology. 1987;33(6):341–348. doi: 10.1159/000212901. [DOI] [PubMed] [Google Scholar]
  9. Furness J. B., Li Z. S., Young H. M., Förstermann U. Nitric oxide synthase in the enteric nervous system of the guinea-pig: a quantitative description. Cell Tissue Res. 1994 Jul;277(1):139–149. doi: 10.1007/BF00303090. [DOI] [PubMed] [Google Scholar]
  10. Gabella G. Detection of nerve cells by a histochemical technic. Experientia. 1969 Feb 15;25(2):218–219. doi: 10.1007/BF01899135. [DOI] [PubMed] [Google Scholar]
  11. Gabella G. Fall in the number of myenteric neurons in aging guinea pigs. Gastroenterology. 1989 Jun;96(6):1487–1493. doi: 10.1016/0016-5085(89)90516-7. [DOI] [PubMed] [Google Scholar]
  12. Gabella G. Neuron size and number in the myenteric plexus of the newborn and adult rat. J Anat. 1971 May;109(Pt 1):81–95. [PMC free article] [PubMed] [Google Scholar]
  13. Gabella G. The number of neurons in the small intestine of mice, guinea-pigs and sheep. Neuroscience. 1987 Aug;22(2):737–752. doi: 10.1016/0306-4522(87)90369-1. [DOI] [PubMed] [Google Scholar]
  14. Horowitz M., Maddern G. J., Chatterton B. E., Collins P. J., Harding P. E., Shearman D. J. Changes in gastric emptying rates with age. Clin Sci (Lond) 1984 Aug;67(2):213–218. doi: 10.1042/cs0670213. [DOI] [PubMed] [Google Scholar]
  15. Hosoda S., Bamba T., Nakago S., Fujiyma Y., Senda S., Hirata M. Age-related changes in the gastrointestinal tract. Nutr Rev. 1992 Dec;50(12):374–377. doi: 10.1111/j.1753-4887.1992.tb02484.x. [DOI] [PubMed] [Google Scholar]
  16. Karaosmanoglu T., Aygun B., Wade P. R., 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. Anat Rec. 1996 Apr;244(4):470–480. doi: 10.1002/(SICI)1097-0185(199604)244:4<470::AID-AR5>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  17. Krammer H. J., Karahan S. T., Rumpel E., Klinger M., Kühnel W. Immunohistochemical visualization of the enteric nervous system using antibodies against protein gene product (PGP) 9.5. Ann Anat. 1993 Aug;175(4):321–325. doi: 10.1016/s0940-9602(11)80029-4. [DOI] [PubMed] [Google Scholar]
  18. Meciano Filho J., Carvalho V. C., de Souza R. R. Nerve cell loss in the myenteric plexus of the human esophagus in relation to age: a preliminary investigation. Gerontology. 1995;41(1):18–21. doi: 10.1159/000213658. [DOI] [PubMed] [Google Scholar]
  19. Nowak T. V., Harrington B., Kalbfleisch J. Age-related changes in enteric neuromuscular transmission. J Pharmacol Exp Ther. 1990 May;253(2):683–687. [PubMed] [Google Scholar]
  20. Pascual J. I., Insausti R., Gonzalo L. M. The pelvic innervation in the rat: different spinal origin and projections in Sprague-Dawley and Wistar rats. Brain Res. 1989 Feb 20;480(1-2):397–402. doi: 10.1016/0006-8993(89)90742-7. [DOI] [PubMed] [Google Scholar]
  21. Porter A. J., Wattchow D. A., Brookes S. J., Schemann M., Costa M. Choline acetyltransferase immunoreactivity in the human small and large intestine. Gastroenterology. 1996 Aug;111(2):401–408. doi: 10.1053/gast.1996.v111.pm8690205. [DOI] [PubMed] [Google Scholar]
  22. Santer R. M., Baker D. M. Enteric neuron numbers and sizes in Auerbach's plexus in the small and large intestine of adult and aged rats. J Auton Nerv Syst. 1988 Nov;25(1):59–67. doi: 10.1016/0165-1838(88)90008-2. [DOI] [PubMed] [Google Scholar]
  23. Santer R. M. Survival of the population of NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst. 1994 Oct;49(2):115–121. doi: 10.1016/0165-1838(94)90131-7. [DOI] [PubMed] [Google Scholar]
  24. Schemann M., Sann H., Schaaf C., Mäder M. Identification of cholinergic neurons in enteric nervous system by antibodies against choline acetyltransferase. Am J Physiol. 1993 Nov;265(5 Pt 1):G1005–G1009. doi: 10.1152/ajpgi.1993.265.5.G1005. [DOI] [PubMed] [Google Scholar]
  25. Stadtman E. R. Biochemical markers of aging. Exp Gerontol. 1988;23(4-5):327–347. doi: 10.1016/0531-5565(88)90036-8. [DOI] [PubMed] [Google Scholar]
  26. Steele P. A., Brookes S. J., Costa M. Immunohistochemical identification of cholinergic neurons in the myenteric plexus of guinea-pig small intestine. Neuroscience. 1991;45(1):227–239. doi: 10.1016/0306-4522(91)90119-9. [DOI] [PubMed] [Google Scholar]
  27. Thompson R. J., Doran J. F., Jackson P., Dhillon A. P., Rode J. PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983 Nov 14;278(1-2):224–228. doi: 10.1016/0006-8993(83)90241-x. [DOI] [PubMed] [Google Scholar]
  28. Young H. M., Furness J. B., Sewell P., Burcher E. F., Kandiah C. J. Total numbers of neurons in myenteric ganglia of the guinea-pig small intestine. Cell Tissue Res. 1993 Apr;272(1):197–200. doi: 10.1007/BF00323587. [DOI] [PubMed] [Google Scholar]
  29. Yunker A. M., Galligan J. J. Extrinsic denervation increases NADPH diaphorase staining in myenteric nerves of guinea pig ileum. Neurosci Lett. 1994 Feb 14;167(1-2):51–54. doi: 10.1016/0304-3940(94)91025-1. [DOI] [PubMed] [Google Scholar]
  30. de Souza R. R., Moratelli H. B., Borges N., Liberti E. A. Age-induced nerve cell loss in the myenteric plexus of the small intestine in man. Gerontology. 1993;39(4):183–188. doi: 10.1159/000213532. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES