Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish

Inflammatory bowel disease (IBD) includes inflammation of the gastrointestinal (GI) tract and is characterized by periods of acute inflammation and remission. Therapeutic management of IBD is still problematic, because of incomplete understanding its pathogenesis. This study focuses on the effect of...

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Main Authors: Leen Uyttebroek, Casper Pype, Guy Hubens, Jean-Pierre Timmermans, Luc van Nassauw
Format: Article
Language:English
Published: PAGEPress Publications 2020-08-01
Series:European Journal of Histochemistry
Subjects:
Online Access:https://ejh.it/index.php/ejh/article/view/3161
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author Leen Uyttebroek
Casper Pype
Guy Hubens
Jean-Pierre Timmermans
Luc van Nassauw
author_facet Leen Uyttebroek
Casper Pype
Guy Hubens
Jean-Pierre Timmermans
Luc van Nassauw
author_sort Leen Uyttebroek
collection DOAJ
description Inflammatory bowel disease (IBD) includes inflammation of the gastrointestinal (GI) tract and is characterized by periods of acute inflammation and remission. Therapeutic management of IBD is still problematic, because of incomplete understanding its pathogenesis. This study focuses on the effect of 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis on changes in enteric neuronal subpopulations in adult zebrafish. These changes are suggested to be related to the altered neuro-immune interactions and GI motility, and in IBD pathogenesis. New insights into neuroplasticity will be instrumental in finding appropriate therapeutic treatments. TNBS was intraluminally administered in the distal intestine (DI) of anesthetized adult zebrafish. A histological time course of the intestinal inflammatory response was created to establish optimal TNBS concentration and acute inflammation phase. Using double immunolabelling on whole mounts, the effect of inflammation on neuronal populations was analyzed. Based on intestinal wall thickening, epithelial fold disruption, reduced goblet cell number, and eosinophil infiltration, our analysis indicated that the optimal TNBS concentration (320 mM in 25% ethanol) inducing non-lethal inflammation reached a peak at 6 hours post-induction. The inflammatory response returned to baseline values at 3 days post-induction. At the acute inflammation phase, no influence on the distribution or proportion of nitrergic neurons was observed, while only the proportion of cholinergic neurons was significantly reduced in the DI. The proportion of serotonergic neurons was significantly increased in the entire intestine during inflammation. This study describes a method of TNBS-induced colitis in the adult zebrafish. Given that the acute inflammation phase is accompanied by neuroplasticity comparable to changes observed in IBD patients, and the unique and versatile characteristics of the zebrafish, allows this model to be used alongside IBD animal models to unravel IBD pathology and to test new IBD therapies.
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spelling doaj.art-e0be6a5dc844457a8a91f7d0e70e15052022-12-22T02:12:24ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062020-08-0164310.4081/ejh.2020.3161Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafishLeen Uyttebroek0Casper Pype1Guy Hubens2Jean-Pierre Timmermans3Luc van Nassauw4Laboratory of Human Anatomy, Faculty of Medicine and Health Sciences, University of AntwerpLaboratory of Applied Veterinary Morphology, Department of Veterinary Sciences, University of AntwerpLaboratory of Human Anatomy, Faculty of Medicine and Health Sciences, University of AntwerpLaboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of AntwerpLaboratory of Human Anatomy, Faculty of Medicine and Health Sciences, University of AntwerpInflammatory bowel disease (IBD) includes inflammation of the gastrointestinal (GI) tract and is characterized by periods of acute inflammation and remission. Therapeutic management of IBD is still problematic, because of incomplete understanding its pathogenesis. This study focuses on the effect of 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis on changes in enteric neuronal subpopulations in adult zebrafish. These changes are suggested to be related to the altered neuro-immune interactions and GI motility, and in IBD pathogenesis. New insights into neuroplasticity will be instrumental in finding appropriate therapeutic treatments. TNBS was intraluminally administered in the distal intestine (DI) of anesthetized adult zebrafish. A histological time course of the intestinal inflammatory response was created to establish optimal TNBS concentration and acute inflammation phase. Using double immunolabelling on whole mounts, the effect of inflammation on neuronal populations was analyzed. Based on intestinal wall thickening, epithelial fold disruption, reduced goblet cell number, and eosinophil infiltration, our analysis indicated that the optimal TNBS concentration (320 mM in 25% ethanol) inducing non-lethal inflammation reached a peak at 6 hours post-induction. The inflammatory response returned to baseline values at 3 days post-induction. At the acute inflammation phase, no influence on the distribution or proportion of nitrergic neurons was observed, while only the proportion of cholinergic neurons was significantly reduced in the DI. The proportion of serotonergic neurons was significantly increased in the entire intestine during inflammation. This study describes a method of TNBS-induced colitis in the adult zebrafish. Given that the acute inflammation phase is accompanied by neuroplasticity comparable to changes observed in IBD patients, and the unique and versatile characteristics of the zebrafish, allows this model to be used alongside IBD animal models to unravel IBD pathology and to test new IBD therapies.https://ejh.it/index.php/ejh/article/view/3161TNBS-induced colitiszebrafishenteric nervous systemserotonergic neuronscholinergic neuronsnitrergic neurons
spellingShingle Leen Uyttebroek
Casper Pype
Guy Hubens
Jean-Pierre Timmermans
Luc van Nassauw
Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
European Journal of Histochemistry
TNBS-induced colitis
zebrafish
enteric nervous system
serotonergic neurons
cholinergic neurons
nitrergic neurons
title Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
title_full Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
title_fullStr Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
title_full_unstemmed Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
title_short Effect of TNBS-induced colitis on enteric neuronal subpopulations in adult zebrafish
title_sort effect of tnbs induced colitis on enteric neuronal subpopulations in adult zebrafish
topic TNBS-induced colitis
zebrafish
enteric nervous system
serotonergic neurons
cholinergic neurons
nitrergic neurons
url https://ejh.it/index.php/ejh/article/view/3161
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AT guyhubens effectoftnbsinducedcolitisonentericneuronalsubpopulationsinadultzebrafish
AT jeanpierretimmermans effectoftnbsinducedcolitisonentericneuronalsubpopulationsinadultzebrafish
AT lucvannassauw effectoftnbsinducedcolitisonentericneuronalsubpopulationsinadultzebrafish