The Onset and Progression of Chronic Colitis Parallels Increased Mucosal Serotonin Release via Enterochromaffin Cell Hyperplasia and Downregulation of the Serotonin Reuptake Transporter

Stavely, R, Fraser, S, Sharma, S, Rahman, A, Stojanovska, V, Sakkal, S, Apostolopoulos, V, Bertrand, P and Nurgali, K 2018, 'The Onset and Progression of Chronic Colitis Parallels Increased Mucosal Serotonin Release via Enterochromaffin Cell Hyperplasia and Downregulation of the Serotonin Reuptake Transporter', Inflammatory Bowel Diseases, vol. 24, no. 5, pp. 1021-1034.


Document type: Journal Article
Collection: Journal Articles

Title The Onset and Progression of Chronic Colitis Parallels Increased Mucosal Serotonin Release via Enterochromaffin Cell Hyperplasia and Downregulation of the Serotonin Reuptake Transporter
Author(s) Stavely, R
Fraser, S
Sharma, S
Rahman, A
Stojanovska, V
Sakkal, S
Apostolopoulos, V
Bertrand, P
Nurgali, K
Year 2018
Journal name Inflammatory Bowel Diseases
Volume number 24
Issue number 5
Start page 1021
End page 1034
Total pages 14
Publisher Oxford University Press
Abstract Background Serotonin (5-hydroxytryptamine, 5-HT) has been linked with several inflammation-associated intestinal diseases, including ulcerative colitis (UC). The largest pool of 5-HT in the body is in enterochromaffin (EC) cells located throughout the intestinal tract. EC cells are mechanosensitive and detect noxious stimuli, inducing secretion of 5-HT, which plays an important role in enteric reflexes and immunomodulation. In this study, we evaluated intestinal 5-HT levels in the Winnie mouse model of spontaneous chronic colitis, which closely replicates UC. Methods Real-time electrochemical recordings of 5-HT oxidation currents were obtained from ex vivo preparations of jejunum, ileum, proximal, and distal colon from Winnie (5-25 weeks old) and age matched C57BL/6 mice. EC cells were examined by immunohistochemistry, and the gene expression of tryptophan hydroxylase 1 (5-HT synthesis) and the serotonin reuptake transporter (SERT) were determined by quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). Results Compression-evoked and basal 5-HT concentrations were elevated in the distal and proximal colon of Winnie mice. EC cell hyperplasia and downregulation of SERT on the transcriptional level were identified as mechanisms underlying increased levels of 5-HT. Increase in mucosal 5-HT release was observed at the onset of disease at 7-14 weeks, confirmed by disease activity scores. Furthermore, increases in 5-HT levels and progression of disease activity correlated linearly with age, but not sex. Conclusions Our findings in the Winnie mouse model of spontaneous chronic colitis demonstrate for the first time that the onset and progression of chronic UC-like intestinal inflammation is associated with increased 5-HT levels in the colonic mucosa.
Subject Gastroenterology and Hepatology
Peripheral Nervous System
Keyword(s) 5-HT
IBD
serotonin
ulcerative colitis
Winnie mouse model
DOI - identifier 10.1093/ibd/izy016
Copyright notice © 2018 Crohns & Colitis Foundation. Published by Oxford University Press. All rights reserved.
ISSN 1078-0998
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Altmetric details:
Access Statistics: 13 Abstract Views  -  Detailed Statistics
Created: Tue, 23 Oct 2018, 16:00:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us