Unveiling the neurogenesis defects induced by prenatal alcohol exposure

Prenatal alcohol exposure (PAE) is known to damage the fetal brain and lead to life-long cognitive and behavioral dysfunctions. Alcohol is believed to interfere with the cerebral cortex development in a variety of ways; however, the precise pathophysiological mechanisms underlying alcohol’s actions are yet poorly understood. In this study, we use pregnant mice voluntarily drinking high amounts of alcohol throughout pregnancy as a model of Fetal Alcohol Spectrum Disorder, and showed that mice reach blood alcohol concentration levels comparable to those reported in binge-drinking humans. We investigated the alcohol-dependent corticogenesis defects, by analyzing the survival, proliferation, specification and migration of projection neurons during embryonic development. By using in utero electroporation, we observed delayed neuronal migration in the sensory cortex of alcohol-exposed embryos. We are now studying the different steps of radial migration by using time-lapse imaging in organotypic slices, to precisely define the alcohol-induced defects on radial migration of projection neurons. Moreover, in order to determine whether PAE has a long-term impact on behavior, we investigated tactile sensitivity by using the adhesive removal test. Our preliminary results have shown that alcohol-exposed females exhibit both increased initial contact time (sensory component) and removal time (motor component), compared to control females, but no difference was observed in males, suggesting sex-specific long-lasting impairment of sensory motor cortical regions induced by PAE. We plan to perform additional behavioral tests to evaluate anxiety levels (open-field, elevated-plus maze), and sociability (three chamber test).