title: Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome.
abstract: OBJECTIVE
  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.
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Giovanni
authors: G
authors: Dothel
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Maria Raffaella
authors: MR
authors: Barbaro
authors: Inserm, U913, Institut des Maladies de l'Appareil Digestif du CHU de Nantes; University of Nantes, Nantes, France.
authors: Hélène
authors: H
authors: Boudin
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Valentina
authors: V
authors: Vasina
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Cesare
authors: C
authors: Cremon
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Luciana
authors: L
authors: Gargano
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Lara
authors: L
authors: Bellacosa
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Roberto
authors: R
authors: De Giorgio
authors: Inserm, U913, Institut des Maladies de l'Appareil Digestif du CHU de Nantes; University of Nantes, Nantes, France.
authors: Catherine
authors: C
authors: Le Berre-Scoul
authors: Inserm, U913, Institut des Maladies de l'Appareil Digestif du CHU de Nantes; University of Nantes, Nantes, France.
authors: Philippe
authors: P
authors: Aubert
authors: Inserm, U913, Institut des Maladies de l'Appareil Digestif du CHU de Nantes; University of Nantes, Nantes, France.
authors: Michel
authors: M
authors: Neunlist
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Fabrizio
authors: F
authors: De Ponti
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy.
authors: Vincenzo
authors: V
authors: Stanghellini
authors: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Italy. Electronic address: giovanni.barbara@unibo.it.
authors: Giovanni
authors: G
authors: Barbara
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003106:Colon / Q000294:innervation* / Q000378:metabolism; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000294:innervation* / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism; D009443:Neuritis / Q000378:metabolism / Q000473:pathology*; D055495:Neurogenesis; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein; C502240:NGF protein, human; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D010751:Phosphopyruvate Hydratase
keywords: Enteric Nerves; Growth-Associated Protein 43; Mast Cells; Nerve Growth Factor