TY - JOUR
T1 - Pathological remodelling of colonic wall following dopaminergic nigrostriatal neurodegeneration
AU - Pellegrini, Carolina
AU - Ippolito, Chiara
AU - Segnani, Cristina
AU - Dolfi, Amelio
AU - Errede, Mariella
AU - Virgintino, Daniela
AU - Fornai, Matteo
AU - Antonioli, Luca
AU - Garelli, Francesca
AU - Nericcio, Anna
AU - Colucci, Rocchina
AU - Cerri, Silvia
AU - Blandini, Fabio
AU - Blandizzi, Corrado
AU - Bernardini, Nunzia
PY - 2020/6
Y1 - 2020/6
N2 - Background and aim: Patients with Parkinson's disease (PD) are often characterized by functional gastrointestinal disorders. Such disturbances can occur at all stages of PD and precede the typical motor symptoms of the disease by many years. However, the morphological alterations associated with intestinal disturbances in PD are undetermined. This study examined the remodelling of colonic wall in 6-hydroxydopamine (6-OHDA)-induced PD rats. Methods: 8 weeks after 6-OHDA injection animals were sacrificed. Inflammatory infiltrates, collagen deposition and remodelling of intestinal epithelial barrier and tunica muscularis in the colonic wall were assessed by histochemistry, immunohistochemistry, immunofluorescence and western blot analysis. Results: 6-OHDA rats displayed significant alterations of colonic tissues as compared with controls. Signs of mild inflammation (eosinophil infiltration) and a transmural deposition of collagen fibres were observed. Superficial colonic layers were characterized by severe morphological alterations. In particular, lining epithelial cells displayed a reduced claudin-1 and transmembrane 16A/Anoctamin 1 (TMEM16A/ANO1) expression; goblet cells increased their mucin expression; colonic crypts were characterized by an increase in proliferating epithelial cells; the density of S100-positive glial cells and vimentin-positive fibroblast-like cells was increased as well. Several changes were found in the tunica muscularis: downregulation of α-smooth muscle actin/desmin expression and increased proliferation of smooth muscle cells; increased vimentin expression and proliferative phenotype in myenteric ganglia; reduction of interstitial cells of Cajal (ICCs) density. Conclusions: A pathological remodelling occurs in the colon of 6-OHDA rats. The main changes include: enhanced fibrotic deposition; alterations of the epithelial barrier; activation of mucosal defense; reduction of ICCs. These results indicate that central nigrostriatal denervation is associated with histological changes in the large bowel at mucosal, submucosal and muscular level. These alterations might represent morphological correlates of digestive symptoms in PD.
AB - Background and aim: Patients with Parkinson's disease (PD) are often characterized by functional gastrointestinal disorders. Such disturbances can occur at all stages of PD and precede the typical motor symptoms of the disease by many years. However, the morphological alterations associated with intestinal disturbances in PD are undetermined. This study examined the remodelling of colonic wall in 6-hydroxydopamine (6-OHDA)-induced PD rats. Methods: 8 weeks after 6-OHDA injection animals were sacrificed. Inflammatory infiltrates, collagen deposition and remodelling of intestinal epithelial barrier and tunica muscularis in the colonic wall were assessed by histochemistry, immunohistochemistry, immunofluorescence and western blot analysis. Results: 6-OHDA rats displayed significant alterations of colonic tissues as compared with controls. Signs of mild inflammation (eosinophil infiltration) and a transmural deposition of collagen fibres were observed. Superficial colonic layers were characterized by severe morphological alterations. In particular, lining epithelial cells displayed a reduced claudin-1 and transmembrane 16A/Anoctamin 1 (TMEM16A/ANO1) expression; goblet cells increased their mucin expression; colonic crypts were characterized by an increase in proliferating epithelial cells; the density of S100-positive glial cells and vimentin-positive fibroblast-like cells was increased as well. Several changes were found in the tunica muscularis: downregulation of α-smooth muscle actin/desmin expression and increased proliferation of smooth muscle cells; increased vimentin expression and proliferative phenotype in myenteric ganglia; reduction of interstitial cells of Cajal (ICCs) density. Conclusions: A pathological remodelling occurs in the colon of 6-OHDA rats. The main changes include: enhanced fibrotic deposition; alterations of the epithelial barrier; activation of mucosal defense; reduction of ICCs. These results indicate that central nigrostriatal denervation is associated with histological changes in the large bowel at mucosal, submucosal and muscular level. These alterations might represent morphological correlates of digestive symptoms in PD.
KW - 6-hydroxydopamine
KW - Collagen deposition
KW - Colon
KW - Histochemistry
KW - Immunofluorescence
KW - Immunohistochemistry
KW - Intestinal dysfunctions
KW - Morphological remodelling
KW - Parkinson's disease
KW - Rat model
UR - http://www.scopus.com/inward/record.url?scp=85080983253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85080983253&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2020.104821
DO - 10.1016/j.nbd.2020.104821
M3 - Article
C2 - 32088380
AN - SCOPUS:85080983253
VL - 139
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
M1 - 104821
ER -