Related Experiment Video
Updated: Aug 17, 2026
Visualization of Estrogen Receptors in Colons of Mice with TNBS-Induced Crohn's Disease using Immunofluorescence
Published on: March 12, 2020
The TNF-α antagonist etanercept reverses age-related decreases in colonic SERT expression and faecal output in mice
Bhavik Anil Patel1, Sara Fidalgo1, Chunfang Wang2
1School of Pharmacy and Biomolecular Science, University of Brighton, Brighton, BN2 4GJ, UK.
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.
Insights
Age-related chronic constipation in mice is linked to changes in serotonin (5-HT) signaling and increased TNF-α. Inhibiting TNF-α with etanercept reversed these changes, suggesting anti-TNF-α drugs may treat constipation in older adults.
Area of Science:
- Gastroenterology
- Aging Research
- Pharmacology
Background:
- Chronic constipation significantly impacts the quality of life for older adults.
- Understanding the underlying causes of age-related constipation is crucial for developing effective treatments.
- Serotonin (5-HT) plays a key role in colonic motility.
Purpose of the Study:
- To investigate if altered colonic 5-HT signaling contributes to age-related changes in fecal output in mice.
- To determine if increased Tumor Necrosis Factor-alpha (TNF-α) is responsible for these age-related signaling changes.
- To explore the therapeutic potential of TNF-α inhibition for age-related constipation.
Main Methods:
- Examined 5-HT signaling components (5-HT, 5-HIAA, SERT) and TNF-α expression in the colons of mice aged 3 to 24 months.
- Monitored fecal output and water content under control conditions.
- Administered etanercept (a TNF-α inhibitor) to aged mice and observed its effects.
Main Results:
- Aged mice exhibited reduced fecal output and water content.
- Aging increased mucosal 5-HT availability and TNF-α expression.
- Aging decreased mucosal SERT expression and 5-HIAA levels.
- Etanercept treatment in aged mice normalized 5-HT signaling components and improved fecal output and water content.
Conclusions:
- Age-related increases in TNF-α expression are key regulators of colonic 5-HT signaling and fecal output in mice.
- These findings suggest that TNF-α plays a significant role in the pathophysiology of constipation in aging.
- Anti-TNF-α therapies show promise as a potential treatment strategy for chronic constipation in the elderly.
