Fetal Alcohol Effects and Choline Intervention

PROJECT SUMMARY Prenatal alcohol exposure can disrupt normal development, leading to a host of pathologies that can include facial dysmorphology, growth deficiencies, and central nervous system dysfunction. Compromised brain development and reduced cognitive capacity are among some of the most devastating of alcohol's adverse effects. Although alcohol-related neurodevelopmental disorders are completely preventable, 2-5% of live births in the U.S. are affected by prenatal alcohol exposure, with even higher rates among some populations. Thus, it is critical that we identify effective treatments and interventions for reducing the adverse consequences of prenatal alcohol exposure, including compromised neuronal plasticity in the offspring. Using a rat model, we have found that supplementation with the nutrient choline can reduce the severity of cognitive deficits associated with developmental alcohol exposure. These benefits are observed even when choline is administered postnatally and after alcohol exposure has ceased. Specifically, we have found that choline supplementation up to postnatal day (PD) 30 reduces the severity of alcohol-induced behavioral deficits on tasks that depend on the functional integrity of the hippocampus. This proposal will examine whether postnatal choline supplementation mitigates alcohol's effects on hippocampal structural and functional plasticity, including adult neurogenesis and long-term potentiation, and if choline enhances other experience-dependent plasticity. We will further investigate whether changes in functional plasticity are related to choline-induced changes in long-lasting cholinergic functioning. In addition, recent data indicate that toddlers and children with fetal alcohol spectrum disorders (FASD) are not consuming adequate amounts of choline and that dietary choline intake correlates with some behavioral outcomes. Thus, we will also determine the effects of postnatal choline deficiency on behavioral development and hippocampal plasticity. Elucidation of choline's effects on brain function and plasticity is critical as choline intervention is already being translated to clinical populations. These studies will not only determine the neural substrates of choline's actions, but also determine if combination therapies are more effective in improving behavioral outcome. Moreover, these studies will help determine if dietary intake among children with FASD influences cognitive functioning. Thus, these studies have important implications for the treatment of FASD.