Nutrient combination to mitigate Fetal Alcohol Spectrum Disorder

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Abstract 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.