PHARMACOLOGY AND CELL METABOLISM Prenatal Alcohol Exposure Induces Long-Term Changes in Dendritic Spines and Synapses in the Mouse Visual Cortex

Aims: To study the long-term changes of dendritic spine and synapse taking place in a mouse model of fetal alcohol spectrum disorders (FASDs). Methods: Pregnant mice were intubated daily with ethanol (EtOH) from E5 to parturition. A DiI diolistic method was used to label dendritic spines of pyramidal cells in the visual cortex of EtOH-exposed and control pups over the period from postnatal (P) day P0 to P30; synaptic ultrastructure was also analyzed using transmission electron microscopy. Results: Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length. The changes were dose dependent and persisted to P30. Ultrastructural changes were also ob- served, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls; ultrastructural changes also persisted to P30. Conclusions: Prenatal alcohol exposure is associated with long- term changes in dendritic spines and synaptic ultrastructure; these alterations probably reflect the developmental retardation of dendritic spines and synapses in visual cortex. These long-term changes are likely to contribute to lifelong mental retardation associated with childhood FASDs.