Impaired cognitive function and altered dendritic morphology of hippocampal neurons in a mouse model of fetal alcohol spectrum disorder.

Prenatal ethanol exposure is a leading preventable cause of neurodevelopmental disability, clinically categorized under fetal alcohol spectrum disorders (FASD). This study explores how developmental alcohol exposure affects the dendritic morphology of hippocampal pyramidal neurons, focusing on the actin cytoskeleton's dynamics essential for neuronal structure and synaptic function. Within this context, we hypothesized that developmental alcohol exposure disrupts actin cytoskeleton dynamics, leading to cognitive deficits and dendritic remodeling in the hippocampus. Neonatal mice (C57BL/6 J) were administered ethanol (5.0 g/kg) intraperitoneally from postnatal day 2-8, establishing a third trimester-equivalent alcohol exposure FASD model. At postnatal day 28, cognitive performance was evaluated using novel location recognition (NLR), novel object recognition (NOR), and the Morris water maze (MWM). Golgi staining assessed dendritic morphology in the hippocampal CA1 region, and the ratio of polymerized (F-actin) to globular actin (G-actin) was measured using a biochemical assay. The results revealed that developmental alcohol exposure significantly impaired recognition and spatial memory, as evidenced by decreased performances in the NOR and MWM tests across both sexes. Golgi staining revealed reduced dendritic arborization complexity and spine density in the CA1 region of the hippocampal pyramidal neurons of both male and female juvenile mice. Biochemical analyses further revealed decresed hipocampal F-actin/G-actin ratios and decreased levels of polymerized F-actin in both sexes. These findings underscore the critical role of cytoskeletal integrity in cognitive development and highlight potential targets for therapeutic intervention in FASD.