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The TNF-α antagonist etanerceptreverses age-related decreases in colonic SERT expression and faecal output in mice

Patel, Bhavik Anil; Fidalgo, Sara; Wang, Chunfang; Parmar, Leema; Mandona, Kasonde; Panossian, Annabelle; Flint, Melanie S.; Ranson, Richard N.; Saffrey, M. Jill and Yeoman, Mark S. (2017). The TNF-α antagonist etanerceptreverses age-related decreases in colonic SERT expression and faecal output in mice. Scientific reports, 7, article no. 42754.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1038/srep42754
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Abstract

Treatment for chronic constipation in older people is challenging and the condition has a major impact on quality of life. A lack of understanding about the causes of this condition has hampered the development of effective treatments. 5-HT is an important pro-kinetic agent in the colon. We examined whether alterations in colonic 5-HT signalling underlie age–related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. Components of the 5-HT signalling system (5-HT, 5-HIAA, SERT) and TNF-α expression were examined in the distal colon of 3, 12, 18 and 24- month old mice and faecal output and water content monitored under control conditions and following the administration of etanercept (TNF-α inhibitor; 1 mg Kg-1). Faecal output and water content were reduced in aged animals. Age increased mucosal 5-HT availability and TNF-α expression and decreased mucosal SERT expression and 5-HIAA. Etanercept treatment of old mice reversed these changes, suggesting that age-related changes in TNFα expression are an important regulator of mucosal 5-HT signalling and pellet output and water content in old mice. These data point to “anti-TNFα” drugs as potential treatments for age-related chronic constipation.

Item Type: Journal Item
Copyright Holders: 2017 The Authors
ISSN: 2045-2322
Project Funding Details:
Funded Project NameProject IDFunding Body
Integrated analysis of the impact of age-associated neuronal and enteroendocrine changes on normal bowel functionsBB/GO15147/1BBSRC (Biotechnology and Biological Sciences Research Council)
Integrated analysis of the impact of age-associated neuronal and enteroendocrine changes on normal bowel functionsBB/G015988/1BBSRC (Biotechnology and Biological Sciences Research Council)
Extra Information: 12 pp.
Keywords: ageing; intestine; constipation; serotonin
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Related URLs:
Item ID: 48677
Depositing User: Jill Saffrey
Date Deposited: 27 Feb 2017 11:11
Last Modified: 15 May 2017 15:35
URI: http://oro.open.ac.uk/id/eprint/48677
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