Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non‐inflamed rectum of patients with Crohn’s disease

Abstract

Knowledge of the neurochemical coding of submucosal neurones in the human gut is important to assess neuronal changes under pathological conditions. We therefore investigated transmitter colocalization patterns in rectal submucosal neurones in normal tissue (n=11) and in noninflamed tissue of Crohn's disease (CD) patients (n=17). Neurone-specific enolase (NSE), choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), substance P (SP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) were detected immunohistochemically in whole-mount preparations from rectal biopsies. The neuronal marker NSE revealed no differences in the number of cells per ganglion (controls 5.0; CD 5.1). Four cell populations with distinct neurochemical codes were identified. The sizes of the populations ChAT/VIP (58% vs. 55%), ChAT/SP (8% vs. 8%), and ChAT/- (22% vs. 22%) were similar in control and CD. The population VIP/- was significantly increased in CD (12% vs. 2% in controls). Unlike in controls, all NOS neurones colocalized ChAT in CD. Thickened CGRP-fibres occurred in CD. We identified neurochemically distinct populations in the human submucous plexus. The increase in the VIP/- population, extensive colocalization of ChAT and NOS and hypertrophied CGRP fibres indicated adaptive changes in the enteric nervous system in noninflamed rectum of CD patients.

III. Imaging and the gastrointestinal tract: mapping the human enteric nervous system

“…The proportion of neurons with a particular neurochemical code was in good agreement with a previous study (15), indicating that there was no experimental bias in that VSD may preferentially label a certain neuronal population. A potential problem is that the quality of the immunohistochemistry decreased with longer recording periods.…”

Role of Na+/H+Exchanger Isoform-1 in Human Inflammatory Bowel Disease

“…Homeostasis of these ions is compromised in inflammatory bowel disease (IBD), leading to motility dysfunctions, diarrhea and pain (1)(2)(3)(4). IBD includes ulcerative colitis (UC) and Crohn's disease (CD).…”

GLP-2: What do we know? What are we going to discover?

“…The direct contact of luminal nutrients with L cells induces the second peak of GLP-2 secretion [65]. Over time it has been observed that patients with intestinal inflammation have changes in the pattern of encoding neurons [66,67] which may be signalled by a reduction in ongoing endogenous GLP-2. Therefore, it is priority to fully elucidate the release mechanism of native GLP-2 in order to optimize it.…”