Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term used to describe the range of outcomes that result from prenatal exposure to alcohol (ethanol). Behavioral effects may include hyperactivity, attention deficit, impaired sensory processing, and learning and memory problems. People with FASDs may also have difficulties using information flexibly, and this could contribute to deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex, but also require hippocampal input. Devising new strategies for amelioration of these problems has great clinical relevance. Given that deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we examine cognitive flexibility (the ability to ?switch mental gears?) in young adults. We propose to continue using our innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline working (short term) memory training during adolescence. The combination of choline + training improves the alcohol-induced deficit in cognitive flexibility but not to the point that performance is equivalent to control animals. In this proposal, we plan to use a mixture of nutrients (that includes choline) that has been shown to provide substrate for dendritic spines in animals and to improve cognitive performance in developing and aging humans. We will assess behavior and brain synaptic protein expression to determine whether our intervention can improve both memory and problem solving and how the effects manifest in the brain in the same animals.

Public Health Relevance

One feature of Fetal Alcohol Spectrum Disorder (FASD) is a deficit in cognition. One of the few nutrients in clinical trials for FASD is choline, however, it is not as effective as hoped. The experiments in this supplement will examine whether a combination of choline plus other nutrients, with or without behavioral training, given during the rat equivalent of late childhood and adolescence will facilitate cognitive function in ethanol-exposed animals in young adulthood. These studies may contribute to devise therapeutic interventions that may alleviate morbidity in FASD.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Grakalic, Ivana
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University of North Carolina Chapel Hill
Schools of Public Health
Chapel Hill
United States
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Akinmboni, T O; Davis, N L; Falck, A J et al. (2018) Excipient exposure in very low birth weight preterm neonates. J Perinatol 38:169-174
Waddell, Jaylyn; Mooney, Sandra M (2017) Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol. Nutrients 9: