How early life experiences shape the brain: behavioral and molecular insights

This thesis explores the profound effects of early life experiences on neurodevelopment, emphasizing the interaction between environmental factors and neuroplasticity. Early life adversity (ELA), including prenatal stress and inadequate maternal care, affects key stress-related neural circuits, particularly in the amygdala (AMY) and prefrontal cortex (PFC). These experiences can increase vulnerability to psychiatric disorders or promote resilience. Additionally, maternal factors, such as nutrition and substance use, significantly shape fetal brain development. The first aim was to investigate how early social environments influence emotional development and stress regulation, focusing on potential sex differences. Juvenile and adult Wistar rats were exposed to either early social isolation (ESI) from postnatal day (PND) 14-21 or communal nesting (CN), a supportive caregiving environment. Molecular assessments of glucocorticoid receptors (GR), cannabinoid receptor type-1 (CB1R), and fatty acid amide hydrolase (FAAH) in the PFC and AMY at PND 35 and PND 75 revealed significant behavioral, emotional, and molecular alterations. Results highlighted sexually dimorphic changes in CB1R expression and glucocorticoid levels, underscoring the importance of sex differences in neurodevelopmental outcomes. The second aim was to examine the effects of prenatal cannabinoid exposure (PCE) on offspring development. Using a novel vaping model to simulate cannabis inhalation, Long-Evans pregnant rats were exposed to THC (50 mg/mL) and CBD (5 mg/mL) from gestational day (GD) 5 to GD20. Behavioral and molecular analyses in offspring revealed significant disruptions in emotional and social behaviors, alongside alterations in AMY transcriptome and glucocorticoid signaling. These findings highlight the long-term impact of early life experiences on neurodevelopment, emphasizing the role of environmental and prenatal influences in shaping susceptibility to psychiatric disorders.