Inhibition of bone morphogenetic protein 4 signaling promotes resilience to depressive-like behavior in the offsprings induced by prenatal stress.

The offspring has different responses to maternal prenatal stress, some susceptible ones exhibit depression or anxiety-like behavior, and some ones demonstrate resilience and do not go on to develop behavior disorders. However, the mechanism underlying the resilience in the offspring to maternal prenatal stress remains unclear. In this study, we aimed to explore whether BMP4 signaling was associated with resilience to depression in the offspring following maternal prenatal stress, and further to explore whether inhibition of BMP4 signaling could promote resilience to depression in the offspring. The pregnant rats were performed mild restraint stress model. After delivery, sucrose preference test, open field test and forced swimming test were used to assess susceptibility or resilience in the offspring. BMP4 inhibitor noggin was administrated to inhibit BMP4 signaling. Hippocampal BMP4- phospho-Smad1/5/8-Id2 signaling and noggin level were measured by RT-PCR and Western Blot Analysis. Immunohistochemistry was used to measure the hippocampal neurogenesis. We found that hippocampal BMP4, phospho-Smad1/5/8 and Id2 level in susceptible offspring rats were significantly higher than that in resilience group. There was less number of BrdU+/NeuN+ positive cells in the dentate gyrus of the hippocampus in susceptible offspring rats than that in resilience group. Administration of BMP4 inhibitor noggin to the pregnant rats suffering from restraint stress could result in an increase of the resilient offspring rats from 16.67% (5/30) to 56.67% (17/30). These observations indicate that BMP4 signaling may be a potential target for promoting resilience to depression for the offspring from maternal prenatal stress.