title: Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress.
abstract: Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.
authors.affiliation: Digestive Diseases Research Unit, Lab Neuro-Immuno-Gastroenterology, Institut de Recerca Vall d'Hebron, CIBERehd, Department of Gastroenterology, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vicario
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Pinchang
authors.initials: P
authors.lastname: Yang
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez
authors.forename: Laura
authors.initials: L
authors.lastname: Ramos
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lobo
authors.forename: Ana
authors.initials: A
authors.lastname: González
authors.forename: Meritxell
authors.initials: M
authors.lastname: Guilà
authors.forename: Marc
authors.initials: M
authors.lastname: Pigrau
authors.forename: Esteban
authors.initials: E
authors.lastname: Saperas
authors.forename: Fernando
authors.initials: F
authors.lastname: Azpiroz
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
mesh_terms: D000818:Animals; D002452:Cell Count; D003106:Colon / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone; D003441:Crowding / Q000523:psychology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006799:Housing, Animal; D007082:Ileum / Q000276:immunology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000276:immunology / Q000523:psychology; D007583:Jejunum / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008928:Mitochondria / Q000378:metabolism; D010539:Permeability; D051381:Rats; D011921:Rats, Inbred WKY; D012931:Social Environment; D013315:Stress, Psychological / Q000209:etiology / Q000276:immunology*; D013997:Time Factors
chemical_list: D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone