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Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice
Abstract
Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.
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“Lastly, higher levels of 5′-HT in children with ASD can be linked to intestinal inflammation and play an important role in intestinal inflammatory responses [200], so there is a connection between enteric serotonin production and dysbiosis.”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [200]
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Metadata
- Authors
- Bischoff, S. C., Mailer, R., Pabst, O., Weier, G., Sedlik, W., Li, Z., Chen, J. J., Murphy, D. L., & Gershon, M. D.
- Affiliations
- University of Hohenheim (DE)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2009-03
- Volume
- 296
- Issue
- 3
- Pages
- G685-G695
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W1997066133
- Cited by
- 206
- References
- 63
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 14 · 2023: 11 · 2022: 13 · 2021: 15 · 2020: 17 · 2019: 8 · 2018: 17 · 2017: 13 · 2016: 18 · 2015: 8 · 2014: 14 · 2013: 9 · 2012: 14
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- serotonin, serotonin transporter, intestinal inflammation, TNBS-induced colitis, immune-related colitis, enteric nervous system, myeloperoxidase, histamine, colonic motility, serotonergic signaling, knockout mice
- MeSH terms
- Animals, Colitis, Colon, Gastrointestinal Motility, Histamine, Mice, Inbred C57BL, Peroxidase, Rectum, Serotonin, Trinitrobenzenesulfonic Acid, Mice, Knockout, Serotonin Plasma Membrane Transport Proteins, Mice
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