Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
Neurogastroenterol Motil. 2013 Dec;25(12):e780-90. doi: 10.1111/nmo.12202. Epub 2013 Aug 21.
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.
CONCLUSIONS & INFERENCES: 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.
在肠易激综合征（IBS）中，家族聚集和跨代传递很大程度上可能取决于环境因素，但在人类环境中很难确定。因此，我们旨在建立相关的动物模型。我们研究了在没有进一步分离方案的情况下，母体分离（MS）长爪沙鼠是否可以将对压力引起的内脏高敏性的易感性跨代传递，以及如果可以，这种传递是否依赖于母体护理。
在成年期，我们评估了非处理第二代后代（NH-F2）在水回避（WA）前后对扩张的内脏运动反应的变化，这些第二代后代来自之前分离的 MS-F1 母鼠。此外，通过交叉寄养 NH-F1 和 MS-F1 母鼠的 F2 后代，并在成年期进行随后的敏感性测量，评估了母体护理的作用。通过肥大细胞稳定化评估 NH-F2 大鼠应激后高敏性中肥大细胞的作用。
在 MS-F1 母鼠的成年 NH-F2 后代中，80%的大鼠在 WA 后对结直肠扩张的敏感性增加，而 NH-F1 母鼠后代的敏感性增加为 19%。交叉寄养的幼崽适应了寄养母亲的表型：NH-F1 母鼠哺乳的 MS-F1 母鼠后代在成年期对扩张的 WA 后高敏性，反之亦然（分别为 100%和 20%）。在 NH-F2 大鼠中，WA 后高敏性被肥大细胞稳定剂 doxantrazole 逆转。
母体分离诱导的对压力触发的内脏高敏性的易感性在跨代传递，这种传递取决于母体护理。因此，MS 是评估与 IBS 家族聚集相关的环境触发因素的合适模型。
