Dopamine transporter genetic reduction induces morpho-functional changes in the enteric nervous system

Silvia Cerantola, Valentina Caputi, Gabriella Contarini, Maddalena Mereu, Antonella Bertazzo, Annalisa Bosi, Davide Banfi, Dante Mantini, Cristina Giaroni, Maria Cecilia Giron

Research output: Contribution to journalArticlepeer-review

Abstract

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by mod-ulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

Original languageEnglish
Article number465
JournalBiomedicines
Volume9
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Confocal microscopy
  • Dopamine transporter
  • Enteric nervous system
  • Neuromuscular contractil-ity
  • Small intestine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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