Early-life stress and susceptibility to social defeat stress in adults mice

In our work, we assessed the delayed effects of stress early in life on susceptibility to social defeat stress in adults. As a model of chronic stress early in life, prolonged separation pups from their mother (3h per day, from PND2 to PND14) were used. We analyzed three groups of adult males: MS+SDS - mice with history of maternal separation early in life and social defeat stress in adults, SDS - mice with normal rearing early in life and social defeat stress in adults, NS (non stressed) - mice with normal rearing early in life and unstressed in adults. We performed H3K4me3 ChIP-seq and RNA-seq analysis on the same homogenates of cortical tissue, which allowed us firstly to study simultaneously changes in transcriptome and genomic landscape of H3K4me3. We find that stress early in life enhances the effects caused by social defeat stress. Male mice with history of maternal separation in early life and social defeat stress in adulthood demonstrate increased level of corticosterone, anxiety, reduced social behavior and also show specific genome-wide alterations in the gene expression, alternative splicing and H3K4me3 landscape in the prefrontal cortex.