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Background and Aim. Obesity is a metabolic disorder with an increasing incidence in Western countries and childhood. It is characterized by low-grade systemic inflammation and several comorbidities, including alterations of gastrointestinal (GI) functions, which impact negatively on patients’ quality of life. There is currently limited information on the morpho-functional features of the GI tract in obese subjects. Of note, the intestinal barrier function has been found to be altered in obese subjects, even before the occurrence of body weight increase [1]. In this light, the present study was carried out to assess, in a mouse model of diet-induced obesity, whether high fat diet (HFD) is associated with morphological alterations of the colonic mucosal barrier. Methods. C57BL/6 mice (n=5/group) were fed with standard diet (SD, 18% calories from fat) or HFD (60% calories from fat). After 8 weeks, body weight, and levels of blood cholesterol, triglycerides and glucose were evaluated. Malondialdehyde (MDA, colorimetric assay), IL-1β and IL-6 levels (ELISA assays) were examined in colonic tissues. Morphological features of colonic mucosal structures (lining epithelial cells, goblet cells, inflammatory infiltrates and enteric glia) were examined by histochemistry and immunohistochemistry. Results. HFD mice displayed significant differences at both molecular and histomorphological level, as compared with SD animals: increased body weight and blood metabolic indexes; increased MDA, IL-1β and IL-6 levels in colonic tissues; altered pattern of claudin-1 expression along with upregulation of transmembrane 16A protein and induced nitric oxide synthase in the enteric epithelium facing the lumen; increased proliferation rate of crypts; altered composition of goblet cell mucous; mucosal gliosis and infiltrates with mixed inflammatory cells. Conclusions. After 8 weeks, HFD intake led to significant alterations of systemic metabolic indexes, colonic tissue inflammation, and colonic mucosal barrier in obese mice, as compared with controls. Morphological studies can be useful to allow the characterization of histopathological patterns of colonic wall remodelling and inflammation underlying bowel motor dysfunctions associated with obesity., Italian Journal of Anatomy and Embryology, Vol. 122, No. 1 (Supplement) 2017

Inflammatory bowel disease (IBD) are chronic and progressive pathologies associated with invalidating abdominal symptoms and increasing incidence in Western countries. Although fibrostenosis is a rare event in ulcerative colitis [UC], it may evolve to fibrosis in the later stages (1, 2). In the present study we examined the histopathological remodeling of the colonic wall from short- and long-lasting (SL and LL) UC patients. Full-thickness left colonic surgical samples were obtained from non-stenotic SL (≤ 3 years) and LL (≥ 10 years) UC patients with a severe exacerbation of colitis and active disease, without clinical signs of fibrostenosis. Collagen and elastic fibres, vascular networks and parameters of fibrosis have been evaluated by histochemistry, immunohistochemistry, confocal immunofluorescence and/or western blot. For comparison, normal colonic control samples from subjects who underwent surgery for uncomplicated colon cancer and without IBD and diverticular disease, were considered.Both SL- and LL-UC showed a thickening in tunica muscularis and activation of transmural neovessels, with proliferating CD105-positive endothelial cells and activated nestin-positive pericytes, as compared with controls. The colonic wall of LL-UC displayed a significant increase in collagen deposition and fibrotic markers (type I and III collagen, fibronectin, vimentin, RhoA), an enhancement of proliferation (PCNA), a decrease in elastic fibres, together with a fibrotic rearrangement of the tunica muscularis smooth muscle cells. In conclusion, a significant full-thickness remodeling of the colonic wall has been documented in the colonic tissues from both SL-UC and LL-UC, as compared to controls: transmural fibrotic thickening and angiogenesis were found in both UC groups, together with a cellular fibrotic/proliferative switch in the tunica muscularis which occurs in the later stages. These histopathological remodeling may contribute to the reduced elastic properties and tissue stretch capability of the wall, thereby impairing the occurrence of a normal motor activity in these subjects., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

Background and Aim. Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor clinical signs, among which gastrointestinal disturbances represent relevant manifestations [1]. Nevertheless, the morphological alterations associated with intestinal dysfunctions in PD have been barely investigated [2]. The present study was aimed at investigating the remodelling of colonic wall in a rat model of PD with central dopaminergic denervation by intra-nigral injection of the neuro-toxin 6-hydroxydopamine (6-OHDA). Methods. Histopathological analysis of the whole colonic wall was performed 4 and 8 weeks after central 6-OHDA injection. Inflammatory infiltrates, collagen deposition as well as the remodelling of intestinal epithelial barrier and tunica muscularis were examined by microscopic techniques (histochemistry/immunohistochemistry/confocal immunofluorescence). Results. Colonic tissue from 8-week 6-OHDA rats were significantly altered, as compared with controls. The tunica mucosa showed: eosinophil infiltration; altered lining epithelium (reduced claudin-1 and transmembrane 16A protein expression) and goblet cells (increased mucus expression); enhanced glial fibrillar acid protein-positive cells and vimentin-positive fibroblast-like cells. Along with transmural collagen deposition, significant changes were observed also in the tunica muscularis: reduced expression of alpha-smooth muscle actin/desmin and increased proliferation index in smooth muscle cells; increased vimentin expression and proliferative phenotype in myenteric ganglia. Conclusions. A full-thickness structural remodelling occurs in the colon of PD rats 8 weeks after central dopaminergic denervation; the main changes include an alteration of the colonic epithelial barrier along with the activation of the mucosal defence and fibrotic switch of the colonic wall. Overall, these findings suggest that: a) early histological modifications occur in the colon of rats with experimental PD at both mucosal and muscular level; b) these changes and the fibrotic alterations might contribute to bowel motor dysfunctions associated with PD., Italian Journal of Anatomy and Embryology, Vol. 122, No. 1 (Supplement) 2017

Parkinson’s disease (PD) is a degenerative neurological disorder, which is often associated with gastrointestinal disturbances (e.g., constipation and defecatory dysfunctions), whose mechanisms are still unknown [1]. Recently, an inflammatory pathogenesis has been proposed to explain these colonic disorders, but low literature are available. This study aims to analyze whether the central dopaminergic denervation, induced by intranigral injection of 6-hydroxydopamine (6-OHDA), can alter the morphological arrangement of colon in rats. Animals were euthanized 4 and 8 weeks after 6-OHDA injection. Histological, histochemical and immunohistochemical analysis were carried out on formalin-fixed, paraffin-embedded colonic samples in order to evaluate: histology, inflammatory cells (eosinophils and mast cells) and collagen fibers in the whole wall; glial fibrillary acidic protein (GFAP), immunoperoxidase, alpha-smooth muscle actin (alpha-SMA) and vimentin immunofluorescence by confocal microscopy. Malondialdehyde (MDA, colorimetric assay), TNF and IL-1β (ELISA assay) levels were also examined. 6-OHDA-induced nigrostriatal denervation was associated with the following histopathological changes observed in the colonic wall: eosinophil and mast cell infiltration, collagen deposition, activation of myenteric glial cells (GFAP+), increased vimentin immunostaining associated with alpha-SMA decrease in the tunica muscularis, enhanced colonic tissue levels of MDA, TNF and IL-1β. On the basis of the present results it is possible to conclude that the induction of central nigrostriatal dopaminergic denervation is followed by inflammation and fibrotic rearrangement of the colonic wall., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016