The TNF-α antagonist etanercept reverses age-related decreases in colonic SERT expression and faecal output in mice.
Sci Rep
; 7: 42754, 2017 02 15.
Article
em En
| MEDLINE
| ID: mdl-28198447
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Gastrointestinais
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Colo
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Constipação Intestinal
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Proteínas da Membrana Plasmática de Transporte de Serotonina
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Etanercepte
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article