Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation

Abstract

Background Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson’s disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs. both CC and controls. Methods Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole-mounts from PD/CC, CC and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyl-transferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors was also assessed. Key Results Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs. CC or vs. controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs. controls (P<.05). VIP, VIPR1 and VIPR2 mRNA expression was significantly reduced in PD/CC vs. CC and controls (P<.05). Conclusions & Inferences Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally-mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.

Modulation of the main porcine enteric neuropeptides by a single low-dose of lipopolysaccharide (LPS) Salmonella Enteritidis

“…Previous studies described a wide range of pathological processes and toxic chemical compounds have such properties. The most important of them are inflammatory processes [ 8 ], nerve fiber damage [ 16 ], mycotoxins [ 29 , 30 ], extra-intestinal metabolic diseases [ 31 ] and psychiatric and neurodegenerative diseases, such as depression or Parkinson’s disease (PD) [ 32 , 33 ].…”

“…The results of this research indicate that LPS administration caused a decrease in VIP expression in the transverse colon. Similarly, a decrease in the number of enteric neurons of submucosal plexuses containing VIP was detected by colonoscopy in parkinsonian patients with chronic constipation [ 33 ]. Moreover, VIP is a factor that participates in the rescue of enteric neurons from LPS-induced cell death [ 51 ].…”

Mast cell‐nerve interactions correlate with bloating and abdominal pain severity in patients with non‐celiac gluten / wheat sensitivity

“…Submucosal whole mounts were analyzed using a previously validated immunohistochemical protocol . The antibody against neurofilament 220 KDa (NF220 KDa, rabbit polyclonal; 1:500, N4142, Sigma) was used to identify perikarya and nerve fibers (Figure B), and a mouse monoclonal antibody (working dilution 1:1000; MAB1222, Millipore) against the specific human tryptase was used to identify mast cells (Figure B) .…”

“…Based on the similarity of intestinal symptoms in NCG/WS, CD, IBS, and FD, it is conceivable that neuro‐immune interactions between MCs and nerves in the mucosa or submucosa of the upper gut can contribute to symptoms reported by NCG/WS patients. In order to establish whether MC‐nerve interactions occur in NCG/SW patients, this study was designed to investigate the neuro‐immune profile in the duodenal submucosa by exploiting a novel technical approach through which routine biopsies can be processed to separate the mucosa from submucosa . We focused on the duodenal submucosa for the following reasons: (a) The diagnostic workup of patients with NCG/WS may include an upper GI endoscopy in order to show possible changes of duodenal mucosa, where from 26% to 96% of NCG/WS patients show a Marsh 1 degree of lesions at duodenal biopsy histology; (b) duodenal submucosa whole mounts, derived from mucosal separation, show a denser innervation than the few nerve endings detectable in a single biopsy.…”

ACE2 Expression in the Cat and the Tiger Gastrointestinal Tracts

“…Since the antibody anti-ACE2 employed in the present study is human-specific, a human submucosal wholemount preparation of descending colon was used as positive control, previous donator consent. Wholemount preparation was analyzed using prevalidated immunohistochemical protocols (17).…”