Prenatal alcohol exposure remains a leading known cause of neurobehavioral disorders -- the most severe and least amenable to treatment of the known alcohol-related birth defects (ARBD). Much has been learned about ARBDs since they were first described 19 years ago. Opportunities now exist for new and exciting studies in this area ranging from alcohol's effects on embryonic gene transcription to laboratory and clinical tests for attenuating and preventing ARBDs. These research opportunities are the cynosure of the projects and pilot studies contained in this renewal application for a Fetal Alcohol Research Center (FARC) at Wayne State University (WSU). This current proposal involves investigators at WSU and collaborations with investigators at other universities, and provides an optimal environment for an integrated, broad-based, multidisciplinary, multifaceted and focused attack on ARBDs. Three areas of shared resources: Administrative Core (including Data Management, Statistics, Education and Training Components), Clinical Research Core and Laboratory Animal Research Core, make this FARC highly cost-effective and efficient. The breadth and focus of this FARC are reflected in 5 major research components and 4 pilot projects. The 5 components range from molecular mechanistic studies to clinical prevention and include: 1) Studies of GENETIC POLYMORPHISMS in ADH genotype and alcohol intake as determinants of alcohol-related birth defects; 2) Molecular biological studies of alcohol's actions on PRE-IMPLANTATION EMBRYOS and subsequent peri- implantation; 3) Molecular biological, neurophysiological and pharmacological studies of midbrain DOPAMINERGIC NEURAL SYSTEMS affected by in utero alcohol exposure; 4) ATTENUATION of neurobehavioral deficits through postnatal environmental enrichment; and 5) A PREVENTION STRATEGY to reduce alcohol consumption and ARBDs in the clinic. Our pilot projects range from molecular studies to early identification studies and include: a) Studies of alcohol's effects on components of the MYC-GENE family in the developing hippocampus; b) NEURAL CYTOSKELETAL alterations resulting from in utero alcohol exposure; c) The role of SLEEP DISTURBANCES in learning/memory dysfunction associated with in utero alcohol exposure; and d) SCREENING for in utero alcohol exposure via brain stem auditory potentials. The cadre of scientists participating in this FARC includes many experienced in alcohol research and several newly attracted to the field. There are clear plans for and commitment to extensive education and training activities, including sponsorship of regular research conferences. Finally, long term commitment to this research area is demonstrated by plans for studies following up on findings from those initially proposed, as well as entirely new investigations.
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