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.

DOI: https://doi.org/10.1038/srep42754

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.

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About

  • Item ORO ID
  • 48677
  • Item Type
  • Journal Item
  • 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 or School
  • Other Departments > Other Departments
  • Copyright Holders
  • © 2017 The Authors
  • Related URLs
  • Depositing User
  • Jill Saffrey

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