Behavioural and developmental consequences of maternal immune activation in offspring

One of the fundamental questions in basic disease research is how stressors experienced during critical periods influence the development of adult disease. In particular, stressors experienced during pregnancy have been shown to have effects on the propensity to develop cognitive disorders in offspring. But is this because of a change directly affecting brain development in utero or is it because mothers change their parental behaviour in response to stressors, or a combination? Further, what are the mechanisms underlying such effects? The placenta plays a critical role in maternal-fetal interactions and fetal adaptive responses in utero which may lead to a propensity to disease development later on in life. Prior work has indicated that placental development is affected by maternal stressors, but it remains unclear whether and how this may result in cognitive impairment in offspring.

The proposed project seeks to answer these questions by applying a multidisciplinary approach to map functional changes along a developmental timeline that links placental morphological development to offspring traits, achieved by combining experimental studies in a rodent model system with evaluation of placental morphological development, together with parent-offspring behavioural interactions, cognitive and behavioural analyses. This will be combined with histological investigations and molecular array studies. This will also be complemented by a bioinformatics component to unravel the biological pathways and genetic networks of known candidates for placental function and associated behavioural impairments. The project therefore offers broad scientific training that will cover mammalian disease and behaviour research, histology, physiology, molecular biology, genetics and bioinformatics.