title: Susceptibility to stress induced visceral hypersensitivity in maternally separated rats is transferred across generations.
abstract: BACKGROUND
  In irritable bowel syndrome (IBS), familial clustering and transfer across generations may largely depend on environmental factors but this is difficult to establish in the human setting. Therefore, we aimed to set up a relevant animal model. We investigated whether susceptibility to stress induced visceral hypersensitivity in maternally separated (MS) Long Evans rats can be transferred across generations without further separation protocols and, if so, whether this depends on maternal care.
  
  
  METHODS
  At adult age, we evaluated pre- vs post water avoidance (WA) changes in visceromotor response to distension in non-handled second filial generation offspring (NH-F2) of previously separated MS-F1 dams. Furthermore, the role of maternal care was evaluated by cross-fostering F2 offspring of NH-F1 and MS-F1 dams and subsequent sensitivity measurements at adult age. Involvement of mast cells in post stress hypersensitivity of NH-F2 rats was evaluated by mast cell stabilization.
  
  
  RESULTS
  In adult NH-F2 offspring of MS-F1 dams, post-WA hypersensitivity to colorectal distension was observed in 80% of rats compared with 19% in offspring of NH-F1 dams. Cross-fostered pups adapted to the phenotype of the foster mother: pups of NH-F1 dams nursed by MS-F1 dams showed post-WA hypersensitivity to distension at adult age and vice versa (100% and 20% respectively). In NH-F2 rats, post-WA hypersensitivity was reversed by mast cell stabilizer doxantrazole.
  
  
  CONCLUSIONS
  Maternal separated-induced susceptibility to stress-triggered visceral hypersensitivity is transferred across generations and this transfer depends on maternal care. Thus, MS is a suitable model to evaluate environmental triggers relevant to IBS clustering in families.
authors: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors: R M
authors: RM
authors: van den Wijngaard
authors: O I
authors: OI
authors: Stanisor
authors: S A
authors: SA
authors: van Diest
authors: O
authors: O
authors: Welting
authors: M M
authors: MM
authors: Wouters
authors: C
authors: C
authors: Cailotto
authors: W J
authors: WJ
authors: de Jonge
authors: G E
authors: GE
authors: Boeckxstaens
mesh_terms: D000818:Animals; D003106:Colon / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008425:Maternal Behavior; D010375:Pedigree; D051381:Rats; D020318:Rats, Long-Evans; D013315:Stress, Psychological / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D059265:Visceral Pain / Q000503:physiopathology
keywords: clustering in families; irritable bowel syndrome; mast cells; stress; transfer; visceral hypersensitivity