Early maternal separation induces alterations of colonic epithelial permeability and morphology.

Abstract

Early maternal separation could lead to significant intestinal barrier and epithelial dysfunction. However, the exact mechanism remains to be elucidated and need to be investigated. Neonatal C57BL/6 mice were subjected to maternal separation: Maternal separation (MS) daily 3h between postnatal day (PND) 5-9, single separation (SS) 3h on PND 9 and no separation (NS). Colon and ileum permeability was measured by Ussing chamber. Severity of morphological changes in the colon was evaluated by blinded grading of histological stained sections. Trans-epithelial resistance of colon and ileum did not change indicating that the tissues remained intact during the course of the experiment. Permeability of trans-cellular tracer Horseradish peroxidase (HRP) was significantly increased in the colon of MS compared to SS and NS (p<0.05 for SS and p<0.001 for NS), but there was no difference in para-cellular permeability of fluorescein isothiocyanate-conjugated dextran (FD4). However, there was no change in permeability of both HRP and FD4 in the ileum. MS and SS groups had marked intestinal epithelium morphology changes in comparison to controls (p<0.05). These preliminary observations indicate that neonatal maternal separation increases colonic trans-cellular permeability. This increase may be caused by the change of the transmural colonic morphology. The underlying mechanism is unknown and further investigation is necessary as it is of relevance to the development of early intestinal diseases such as necrotizing enterocolitis.