TY - JOUR
T1 - Susceptibility to stress induced visceral hypersensitivity in maternally separated rats is transferred across generations
AU - van den Wijngaard, R. M.
AU - Stanisor, O. I.
AU - van Diest, S. A.
AU - Welting, O.
AU - Wouters, M. M.
AU - Cailotto, C.
AU - de Jonge, W. J.
AU - Boeckxstaens, G. E.
PY - 2013
Y1 - 2013
N2 - 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. 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. 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. 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
AB - 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. 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. 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. 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
U2 - https://doi.org/10.1111/nmo.12202
DO - https://doi.org/10.1111/nmo.12202
M3 - Article
C2 - 23965154
SN - 1350-1925
VL - 25
SP - e780-e790
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 12
ER -