Long-term impact of embryonic ethanol exposure on gene expression and executive functions in zebrafish

This study explores the long-term effects of embryonic ethanol exposure on cognitive functions and gene expression in zebrafish (Danio rerio). We hypothesized that ethanol exposure during a critical developmental stage would lead to deficits in executive functions, such as working memory and behavioral flexibility, as well as alterations in neurodevelopmental gene expression. Zebrafish embryos were exposed to ethanol for 2 h at 24 hpf (hours post fertilization), and behavior was assessed at the fry (15 days post-fertilization), juvenile (45 dpf), and adult (90 dpf) stages. The Y-FMP behavioral test revealed impairments in behavioral flexibility and working memory, indicated by increased repetitive strategy in the juvenile phase and reduced alternation strategy in adult individuals. Molecular analyses showed downregulation of genes responsible for neurodevelopment and also dopaminergic signaling, suggesting that ethanol exposure disrupts critical developmental pathways. Despite partial recovery of gene expression in the juvenile stage, cognitive deficits persisted, highlighting the long-term impact of embryonic ethanol exposure. This study underscores the need for early diagnostic and intervention strategies for individuals affected by Fetal Alcohol Spectrum Disorders (FASD) and calls for further research on biomarkers to distinguish FASD from other neurodevelopmental disorders. In conclusion, our findings demonstrate that embryonic ethanol exposure significantly impacts cognitive functions and gene expression pattern in zebrafish, mirroring the challenges faced by individuals with FASD. These results contribute to the understanding of the neurodevelopmental consequences of prenatal ethanol exposure and reinforce the importance of preventing ethanol consumption during pregnancy.