From the intestinal mucosal barrier to the enteric neuromuscular compartment: an integrated overview on the morphological changes in Parkinson’s disease

Abstract

Gastrointestinal dysfunctions represent the most common non-motor symptoms in Parkinson’s disease (PD). Of note, changes in gut microbiota, impairments of intestinal epithelial barrier (IEB), bowel inflammation and neuroplastic rearrangements of the enteric nervous system (ENS) could be involved in the pathophysiology of the intestinal disturbances in PD. In this context, although several review articles have pooled together evidence on the alterations of enteric bacteria-neuro-immune network in PD, a revision of the literature on the specific morphological changes occurring in the intestinal mucosal barrier, the ENS and enteric muscular layers in PD, is lacking. The present review provides a complete appraisal of the available knowledge on the morphological alterations of intestinal mucosal barrier, with particular focus on IEB, ENS and enteric muscular layers in PD. In particular, our intent was to critically discuss whether, based on evidence from translational studies and pre-clinical models, morphological changes in the intestinal barrier and enteric neuromuscular compartment contribute to the pathophysiology of intestinal dysfunctions occurring in PD.

Enteric Glia and Brain Astroglia: Complex Communication in Health and Disease along the Gut-Brain Axis

“…In this context, preclinical and human studies have reported that IBDs are associated with a hyperactivation of EGCs with an increase in proinflammatory cytokine release, as well as the occurrence of astrogliosis in the hippocampus, documented by the increment of glial marker fibrillary acidic protein (GFAP) expression (Bao and others 2015; D’Antongiovanni, Pellegrini, and others 2020; Do and Woo 2018; Gampierakis and others 2021). Likewise, morphofunctional alterations of astrocytes, observed in neurodegenerative diseases, not only contribute to the central neuroinflammation and neurodegeneration but could also exert alterations of EGCs through brain-gut descending pathways, thus contributing to GI comorbidities associated with such pathologic conditions (D’Antongiovanni, Pellegrini, and others 2020; Nordengen and others 2019; Oksanen and others 2019; Pellegrini and others 2021; Pellegrini and others 2023).…”