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

Patel, Bhavik Anil, Fidalgo, Sara, Wang, Chunfan, Parmar, Leena, Mandona, Kasonde, Panossian, Annabelle, Flint, Melanie, Ranson, Richard, Saffrey, Jill and Yeoman, Mark (2017) The TNF-α antagonist etanercept reverses age-related decreases in colonic SERT expression and faecal output in mice. Scientific Reports, 7. p. 42754. ISSN 2045-2322

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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.

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