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Changes in murine anorectum signaling across the life course

Fidalgo, S.; Patel, B. A.; Ranson, R. N.; Saffrey, M. J. and Yeoman, M. S. (2018). Changes in murine anorectum signaling across the life course. Neurogastroenterology & Motility, 30(10), article no. e13426.

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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.

Item Type: Journal Item
Copyright Holders: 2018 The Authors
ISSN: 1365-2982
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetBB/GO15147/1BBSRC (Biotechnology and Biological Sciences Research Council)
Not SetBB/GO15988/1BBSRC (Biotechnology and Biological Sciences Research Council)
Keywords: aging; fecal impaction; internal anal sphincter; nitric oxide
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 56177
SWORD Depositor: Jisc Publications-Router
Depositing User: Jisc Publications-Router
Date Deposited: 17 Aug 2018 13:18
Last Modified: 13 May 2019 12:52
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