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Authors & Affiliations
Beatrice Dal Bianco, Sowmya Narayan, Carlo Castoldi, Shiladitya Mitra, Mathias Schmidt, Bianca A. Silva
Abstract
Anxiety and mood disorders significantly impact individual well-being and societal health, highlighting the need for a thorough understanding of their risk factors. While early life stress is widely recognized as a risk factor for multiple psychiatric conditions, the neurobiological mechanisms driving these effects are yet to be fully understood.In this collaborative study, we investigated the long-lasting consequences of developmental stress on adult brain function, increasing susceptibility to the aforementioned disorders.To investigate the long-lasting consequences of developmental stress, we administered corticosterone injections to pregnant mice from gestational days 11 to 15 and subjected their offspring to limited bedding and nesting conditions during the early postnatal period (days 2-9). Both female and male adult offspring showed increased depressive- and anxiety-like behavior such as impaired social interaction, lack of motivation, and increased impulsivity. To investigate the neural correlates of these developmental-stress induced deficits, we performed whole-brain cFos mapping following the social interaction test. For this, we used a semi automated pipeline (https://biop.github.io/ijp-imagetoatlas/), recently developed in collaboration with N. Chiarrutini (Biop, EPFL).Interestingly, developmentally stressed male offspring displayed augmented brain activity in the isocortex, thalamus and striatum with respect to the control group, while female offspring exhibited a more heterogeneous pattern of brain activation. Functional connectome analysis further confirmed that developmental stress affects the adult brain networks recruited upon social interactions. Recognizing these sex-dependent responses emphasizes the necessity of incorporating both sexes in pre-clinical studies, providing insights for more effective treatment strategies.