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.

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

Bosi, Annalisa;Banfi, Davide;Giaroni, Cristina
Penultimo
;
2022-01-01

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.
2022
2022
Dopamine; Dopamine transporter; Gastrointestinal tract; Inflammation; Myenteric plexus
Cerantola, Silvia; Faggin, Sofia; Caputi, Valentina; Bosi, Annalisa; Banfi, Davide; Rambaldo, Anna; Porzionato, Andrea; Di Liddo, Rosa; De Caro, Raffaele; Savarino, Edoardo V; Giaroni, Cristina; Giron, Maria Cecilia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2133926
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