Small intestine neuromuscular dysfunction in a mouse model of dextran sulfate sodium-induced ileitis: Involvement of dopaminergic neurotransmission.

Abstract

AIMS:

Anomalies in dopaminergic machinery have been shown in inflammatory bowel disease (IBD) patients and preclinical models of IBD. Thus, we aimed to evaluate the impact of dextran sodium sulfate (DSS)-induced ileitis on enteric dopaminergic pathways.

MATERIALS AND METHODS:

Male C57/Bl6 mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and were then switched to regular drinking water for 3 days. To measure ileitis severity inflammatory cytokines (IL-1β, TNFα, IL-6) levels were assessed. Changes in ileal muscle tension were isometrically recorded following: 1) cumulative addition of dopamine on basal tone (0.1-1000 μM); ii) 4-Hz electric field stimulation (EFS) in the presence of 30 μM dopamine with/without 10 μM SCH-23390 (dopamine D1 receptor (D1R) antagonist) or 10 μM sulpiride (D2R antagonist). Immunofluorescence distribution of the neuronal HuC/D protein, glial S100β marker, D1R, and dopamine transporter (DAT) were determined in longitudinal-muscle-myenteric plexus whole-mounts (LMMPs) by confocal microscopy. D1R and D2R mRNA transcripts were evaluated by qRT-PCR.

KEY FINDINGS:

DSS caused an inflammatory process in the small intestine associated to dysmotility and altered barrier permeability, as suggested by decreased fecal output and enhanced stool water content. DSS treatment caused a significant increase of DAT and D1R myenteric immunoreactivity as well as of D1R and D2R mRNA levels, accompanied by a significant reduction of dopamine-mediated relaxation, involving primarily D1-like receptors.

SIGNIFICANCE:

Mouse ileitis affects enteric dopaminergic neurotransmission mainly involving D1R-mediated responses. These findings provide novel information on the participation of dopaminergic pathways in IBD-mediated neuromuscular dysfunction.

• Authors: Silvia Cerantola, Sofia Faggin, Valentina Caputi, Annalisa Bosi, Davide Banfi, Anna Rambaldo, Andrea Porzionato, Rosa Di Liddo, Raffaele De Caro, Edoardo V Savarino, Cristina Giaroni, Maria Cecilia Giron
• Journal: Life sciences (Life Sci) Vol. 301 Pg. 120562 (Jul 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35487304 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Dopamine Antagonists
• Drinking Water
• RNA, Messenger
• Receptors, Dopamine D1
• Dextran Sulfate
• Dopamine

Topics

• Animals
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Dopamine
• Dopamine Antagonists
• Drinking Water
• Humans
• Ileitis (chemically induced)
• Inflammatory Bowel Diseases
• Intestine, Small (metabolism)
• Male
• Mice
• RNA, Messenger (genetics)
• Receptors, Dopamine D1 (metabolism)
• Synaptic Transmission (physiology)