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 FASD may also have difficulties using information flexibly which likely underlies deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex. Devising new strategies for amelioration of these problems has great clinical relevance. While deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we will examine cognitive flexibility. We propose an innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline AND behavioral training during adolescence. Either alone can improve learning and memory in normal animals, as well as in models of FASD. We have chosen the attentional set shifting and reversal learning task because it captures deficits reported in clinical observation of individuals with FASD and also because it can be used repeatedly in the same rats without observable diminution of responding or changes in task strategy. We propose a multidisciplinary set of experiments that will assess behavior, brain function and structure, as well as expression of neurometabolites. These experiments will determine whether modulating plasticity during frontal cortex development can improve both memory and problem solving in the same animals and how the effects manifest in brain connectivity and structure.
One feature of Fetal Alcohol Spectrum Disorder (FASD) is a deficit in executive function. The experiments in this grant will examine whether the combination of nutritional intervention, choline supplementation, and behavioral training during the rat equivalent of late childhood and adolescence will facilitate executive function in ethanol-exposed animals in young adulthood. These studies may contribute to devise therapeutic interventions that may alleviate morbidity in FASD.
|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:|