Prenatal alcohol exposure can disrupt development, leading to a spectrum of disorders that include facial dysmorphology, growth deficiencies and central nervous system dysfunction. Alcohol's adverse effect on brain development and consequent cognitive abilities are among the most devastating. Yet, although alcohol- related neurodevelopmental disorders are completely preventable, women continue to drink alcohol during pregnancy. Thus, it is critical that we identify effective treatments and interventions for reducing the adverse consequences of prenatal alcohol exposure. Many behavioral alterations associated with prenatal alcohol exposure may be related to altered cholinergic functioning. Interestingly, perinatal choline supplementation in control subjects can lead to long-lasting enhancements in cholinergic functioning and cognitive abilities. Thus, we hypothesized that perinatal choline supplementation may reduce the severity of some fetal alcohol effects. Using an animal model system, we demonstrated that perinatal choline supplementation attenuates the hyperactivity and learning deficits associated with alcohol exposure during development. In fact, choline supplementation is effective even when administered after the alcohol exposure is complete and during a period of brain development equivalent to early postnatal development in humans. This proposal continues our investigation of choline as a potential treatment for fetal alcohol effects. Using an animal model of third trimester alcohol exposure, we first plan to examine the temporal windows of choline's effectiveness. Elucidation of the developmental periods when choline is effective will produce further hypotheses of its mechanisms of action and indicate if choline can be administered and still be effective later in life. Secondly, we will examine if perinatal choline supplementation leads to long-lasting changes in cholinergic functioning in our alcohol-exposed subjects. This will allow us to correlate behavioral changes with neurochemical substrates. Finally, we will examine if choline supplementation can enhance the efficacy of other behavioral treatments, specifically environmental enrichment. If choline potentiates the effects of environmental enrichment, it would suggest that combinations of treatments may be the most effective for children with FASD. Importantly, choline supplementation may serve as a relatively safe and effective treatment that could be administered after birth in humans.
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