Early-life social and material deprivation drives sex-dependent alterations in social behavior across the lifespan and neuroinflammatory transcriptomic signatures in the prefrontal cortex

Early-life adversities are a major risk factor for later mental health disorders, but the underlying neurobiological mechanisms remain poorly understood. To address this gap, we established a murine model of social and material deprivation (SMD)—combining reduced nesting, maternal separation, early weaning, and social stress—to better reproduce the complexity of human socioeconomic disadvantage. Offspring exposed to SMD displayed delayed growth alongside heightened anxiety- and depression-like behaviors. These functional changes were accompanied by structural alterations, including reductions in hippocampal area and an enlargement of the prefrontal cortex (PFC). Crucially, SMD altered social interactions and dominance patterns in an age- and sex-specific manner. While alterations in juvenile social play were observed exclusively in females, differences in adult sociability were restricted to males. Additionally, adult social memory was altered in both sexes. Beyond sociability, SMD drove a dominant phenotype in both sexes during the tube test, and increased aggressive behavior in males. Seeking molecular correlates within the PFC, we detected altered Pdgfa expression and sex-specific transcriptomic signatures indicative of neuroinflammation, which we are currently evaluating through microglial immunohistochemistry. Altogether, our findings demonstrate that SMD affects neurodevelopment and social behavior through complex, sex-dependent molecular mechanisms.