Maternal adversity and epigenetic and behavioral programming across generations

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DESCRIPTION (provided by applicant): The gestational and postpartum maternal environment plays an important role in developing susceptibility to psychiatric disorders later in life. Although the societal cost of prenatal and postnatal adversity, such as maternal infection and childhood adversity and trauma, is recognized, our understanding of the pathogenesis of these conditions is very limited. By using animal models of maternal adversity, we identified modifications in DNA methylation in specific neurons in the central nervous system that, via the modulation of gene expression, predispose the offspring to anxiety and increased stress responsiveness. These modifications occur at genes that encode proteins involved in synaptogenesis and synaptic functions indicating that the behavioral abnormalities are caused by multiple functional deficits at the synapse. This application will explore the spectrum, specificity, distribution and functional significance of DNA methylation in three different models of maternal adversity with construct validity and how these modifications derail the normal developmental trajectory of neuronal differentiation, synaptogenesis and emotional behavior. These studies will help identifying key neurodevelopmental genes and proteins that can be pharmacologically targeted to prevent or reverse the negative effects of early life adversity.