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

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Patel, Bhavik Anil ; Fidalgo, Sara ; Wang, Chunfang ; Parmar, Leena ; Mandona, Kasonde ; Panossian, Annabelle ; Flint, Melanie S. ; Ranson, Richard N. ; Saffrey, M. Jill ; Yeoman, Mark S. (2017)
  • Publisher: Nature Publishing Group
  • Journal: Scientific Reports, volume 7 (issn: 2045-2322, eissn: 2045-2322)
  • Related identifiers: doi: 10.1038/srep42754, pmc: PMC5309893
  • Subject: C900 | Article

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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