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Gastroenterology. 2015 May;148(5):1002-1011.e4. doi: 10.1053/j.gastro.2015.01.042. Epub 2015 Feb 2.

Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome.

Author information

1
Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
2
Inserm, U913, Institut des Maladies de l'Appareil Digestif du CHU de Nantes; University of Nantes, Nantes, France.
3
Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy. Electronic address: giovanni.barbara@unibo.it.

Abstract

BACKGROUND & AIMS:

Mediators released by the intestinal mucosa of patients with irritable bowel syndrome (IBS) affect the function of enteric and extrinsic sensory nerves, which can contribute to the development of symptoms. Little is known about the effects of mucosal mediators on intestinal neuroplasticity. We investigated how these mediators affect the phenotypes of colonic mucosa nerve fibers, neuron differentiation, and fiber outgrowth.

METHODS:

We analyzed mucosal biopsy samples collected from 101 patients with IBS and 23 asymptomatic healthy individuals (controls). We measured levels of neuronal-specific enolase, growth-associated protein 43, nerve growth factor (NGF), and tyrosine kinase receptor A (NTRK1) by immunohistochemistry and enzyme-linked immunosorbent assay. Primary rat enteric neurons and human SH-SY5Y cells were incubated with supernatants from the mucosal biopsies and analyzed by morphometric and polymerase chain reaction analyses.

RESULTS:

Compared with mucosal tissues of controls, mucosa from patients with IBS had a significant increase in the area of lamina propria occupied by neuronal-specific enolase-positive (57.7% increase) and growth-associated protein 43-positive fibers (56.1% increase) and staining density of NGF (89.3% increase) (P < .05 for all). Levels of NGF protein were also increased in tissues from patients with IBS vs controls (18% increase; P = .16) along with levels of NTRK1 (64% increase; P < .05). Mucosal supernatants from tissues of patients with IBS induced higher levels of neuritogenesis in primary culture of enteric neurons, compared with controls, and more NGF-dependent neuronal sprouting in SH-SY5Y cells.

CONCLUSIONS:

Nerve fiber density and sprouting, as well as expression of NGF and NTRK1, are significantly increased in mucosal tissues of patients with IBS. Mucosal mediators participate to these neuroplastic changes.

KEYWORDS:

Enteric Nerves; Growth-Associated Protein 43; Mast Cells; Nerve Growth Factor

Comment in

PMID:
25655556
DOI:
10.1053/j.gastro.2015.01.042
[Indexed for MEDLINE]

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