NEUROANATOMICAL/FUNCTIONAL CORRELATES IN FASD MODEL

Duke University, Durham NC

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of the proposed research is to characterize the long-term effects on the mouse brain resulting from early gestational ethanol exposure. In spite of the tremendous literature describing the actions of ethanol on the developing nervous system, there is still much to learn, especially regarding the effects of ethanol exposure during early periods of pregnancy. Previous studies examining the effects of early gestational ethanol exposure (during parts of the first trimester equivalent) have demonstrated detrimental effects on specific brain regions (e.g. the cerebellum and hippocampus) and a general somatic growth retardation. To date, research concentration has been on the prenatal manifestations of ethanol dysmorphogenesis, with the long-term developmental profile of these adverse effects remaining unexplored. The work outlined in this proposal will utilize high-resolution magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and a battery of behavioral tests to more fully examine the sequelae of ethanol exposure on gestational day (GD) 8 in C57Bl/6J mice;an exposure time which previous studies have shown to be worthy of in-depth consideration. It is hypothesized that the regional deficits observed and previously reported by the candidate to occur in fetal mice will remain throughout postnatal development, in spite of a reversal of the somatic growth retardation. The results of the experiments proposed herein will greatly expand our knowledge of the long-term effects of early ethanol exposure on both the structure and function of the brain.