Changes in murine anorectum signaling across the life course

Sara Fidalgo, Bhavik Patel, Rachel Ranson, Jill Saffrey, Mark Yeoman

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.
Methods: The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age-related changes in nitric oxide and acetylcholine release.
Key Results: Nitrergic relaxation increased between 3 and 6 months, peaked at
12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age-related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age-related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.
Conclusions and Inferences: The decrease in nitrergic signaling with increasing age may contribute to the age-related fecal impaction and constipation previously described in this model by partially obstructing defecation.
Original languageEnglish
Article numbere13426
Pages (from-to)13426-13438
Number of pages13
JournalNeurogastroenterology and Motility
Volume30
Issue number10
DOIs
Publication statusPublished - 30 Jul 2018

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Fecal Impaction
Acetylcholine
Constipation
Cholinergic Agents
Nitric Oxide
Defecation
Cholinesterases
Nitroprusside
Baths
Smooth Muscle
Adenosine Triphosphate
Incidence

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2018 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons, Ltd

Keywords

  • aging
  • fecal impaction
  • internal anal sphincter
  • nitric oxide

Cite this

Fidalgo, Sara ; Patel, Bhavik ; Ranson, Rachel ; Saffrey, Jill ; Yeoman, Mark. / Changes in murine anorectum signaling across the life course. In: Neurogastroenterology and Motility. 2018 ; Vol. 30, No. 10. pp. 13426-13438.
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Changes in murine anorectum signaling across the life course. / Fidalgo, Sara; Patel, Bhavik; Ranson, Rachel; Saffrey, Jill; Yeoman, Mark.

In: Neurogastroenterology and Motility, Vol. 30, No. 10, e13426, 30.07.2018, p. 13426-13438.

Research output: Contribution to journalArticleResearchpeer-review

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N2 - Background: Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.Methods: The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age-related changes in nitric oxide and acetylcholine release.Key Results: Nitrergic relaxation increased between 3 and 6 months, peaked at12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age-related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age-related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and Inferences: The decrease in nitrergic signaling with increasing age may contribute to the age-related fecal impaction and constipation previously described in this model by partially obstructing defecation.

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