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. Fetal Alcohol Spectrum Disorders (FASD), significant components of which are CNS and craniofacial abnormalities, are a major public health problem. While eliminating FASD is the ultimate goal for clinical and basic FASD research, we recognize that in the near future, adverse effects from prenatal ethanol exposure will persist. To better diagnose and treat affected individuals, a more complete understanding of the full spectrum of the ethanol-induced abnormalities is needed. The proposed investigations are designed to contribute significantly toward meeting this need. For this work, Diffusion Tensor Imaging (DTI), which allows CNS fiber tract analyses at a high resolution (60-micron or less isotropic), will be applied to the study of an FASD mouse model. Previous research using this model established critical exposure times that yield facial and CNS abnormalities consistent with full-blown Fetal Alcohol Syndrome, as well as other components of FASD. The proposed studies will employ this model and both acute and chronic ethanol treatment paradigms to test the overall hypothesis that in mice, ethanol induces structural abnormalities of the brain and face that are consistent with and informative for those in human FASD. To this end, utilizing DTI as high throughput screening platforms, we propose to provide comprehensive documentation and discovery of the ethanol-induced CNS dysmorphology that results from prenatal ethanol exposure at embryonic and early fetal stages of development. It is expected that the structural abnormalities of the brain that are induced by ethanol in mice will reflect the pattern of defects observed in children with FASD, will inform human diagnostic tests, and will provide new information to help reduce the incidence of FASD.
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