Multiple sclerosis (MS) is an autoimmune neurodegenerative and demyelinating disease that affects the central nervous system (CNS). However, numerous recent scientific findings suggest a bidirectional connection between the CNS and the enteric nervous system (ENS) involved in the pathogenesis of this disease. Therefore, this study aims to assess the impact of cuprizone-induced demyelination on the structure and function of the ENS in a murine model of MS. In vivo and ex vivo analyses of small intestine contractile functionality were conducted, and in vitro analyses were performed through confocal microscopy to evaluate the presence of structural alterations in the neuroglial network of the ENS caused by toxic demyelination. Finally, quantitative analysis using RT-qPCR assessed the expression of a gene pool in specific brain areas and the ileum. This research provides important insights into better understanding the link between MS and gastrointestinal disorders, opening new perspectives for further studies and the identification of potential therapeutic targets to improve the quality of life of MS patients and their associated intestinal symptoms.
La sclerosi multipla (SM) è una malattia neurodegenerativa e demielinizzante di origine autoimmune che colpisce il sistema nervoso centrale (SNC). Tuttavia numerose evidenze scientifiche recenti suggeriscono una connessione bidirezionali tra il SNC e il sistema nervoso enterico (SNE) coinvolte nella patogenesi di questa malattia. Questo studio, quindi, mira a valutare l’impatto della demielinizzazione indotta dalla neurotossina cuprizone sulla struttura e funzione del SNE in un modello murino di SM. Sono state condotte analisi in vivo ed ex vivo della funzionalità contrattile del piccolo intestino e analisi in vitro attraverso microscopia confocale per valutare la presenza di alterazioni strutturali nella rete neurogliale del SNE, causate dalla demielinizzazione tossica. Infine attraverso analisi quantitativa con RT-qPCR è stata valutata l’espressione di un pool di geni in specifiche aree celebrali ed ileo. Questa ricerca fornisce importanti spunti per comprendere meglio il legame tra la SM e i disturbi gastrointestinali, aprendo nuove prospettive per ulteriori studi e l'identificazione di potenziali bersagli terapeutici per migliorare la qualità di vita dei pazienti con SM e i relativi sintomi intestinali.
Valutazione delle alterazioni sulla struttura e funzione del sistema nervoso enterico in un modello murino di sclerosi multipla
PRIORE, ANTONIO
2023/2024
Abstract
Multiple sclerosis (MS) is an autoimmune neurodegenerative and demyelinating disease that affects the central nervous system (CNS). However, numerous recent scientific findings suggest a bidirectional connection between the CNS and the enteric nervous system (ENS) involved in the pathogenesis of this disease. Therefore, this study aims to assess the impact of cuprizone-induced demyelination on the structure and function of the ENS in a murine model of MS. In vivo and ex vivo analyses of small intestine contractile functionality were conducted, and in vitro analyses were performed through confocal microscopy to evaluate the presence of structural alterations in the neuroglial network of the ENS caused by toxic demyelination. Finally, quantitative analysis using RT-qPCR assessed the expression of a gene pool in specific brain areas and the ileum. This research provides important insights into better understanding the link between MS and gastrointestinal disorders, opening new perspectives for further studies and the identification of potential therapeutic targets to improve the quality of life of MS patients and their associated intestinal symptoms.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/64093