While exposure to early life stress (ELS) represents a key etiological element for the development of psychiatric disorders, the
mechanisms underlying such link are poorly understood. With this respect, animal models represent unique tools to identify
ELS-induced alterations and their association with psychopathological outcomes. To this regard, our project will employ two different
well-established models of ELS: i) the model of prenatal stress (PNS) that mimics exposure to adversities during gestation and may
also reflect the presence of emotional liability during such time frame, and ii) the paradigm of social isolation from weaning
mimicking a deprivation form social interaction that is critical during the maturation stages across adolescence. The aims of our
project will be to: i) provide novel information on vulnerability and resilience to ELS for selected psychopathologic domains, also
considering the biological sex as a relevant variable; ii) characterize the molecular underpinnings for susceptibility or resilience to
stress, with a focus on selected brain regions (including prefrontal cortex, nucleus accumbens, amygdala, and dorsal/ventral
hippocampus); iii) investigate the connectivity within specific brain circuits in determining stress-induced functional impairment or
resilience by exposing the animals to challenging conditions that activate specific circuits and molecular mechanisms; iv) investigate
whether exposure to ELS may predispose to psychopathological states following an immune challenge during different postnatal
periods.
Our results will represent an important step forward in understanding the association between stress exposure and psychopathologic
domains. Our study will contribute to unraveling novel molecular pathways underlying the development of psychiatric disorders,
which may contribute to the development of innovative strategies for the treatment of stress-induced mental disturbances.
Overall, our study has enormous relevance and implications at the clinical level, as it will expand the knowledge on the etiological
mechanisms contributing to specific psychopathologic domains that are encountered in major depression, a relevant cause of
disability worldwide. Such advancement will ultimately lead to improved functional outcomes for the people suffering from severe
mental disorders.