EFFECTS OF ETHANOL ON GLUCOSE TRANSPORTER EXPRESSION

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The developing brain is extremely sensitive to the toxic effects of ethanol, but the mechanisms underlying these effects are not well understood. It is proposed that exposure of the developing brain to ethanol results in the specific regulation of the glucose transporter isoforms GLUT1 and GLUT3. It is also proposed that alterations in glucose transporter gene expression may be regulated in a regional and or cell-type specific manner at transcriptional or posttranscriptional levels. Changes in glucose transport, resulting from changes in the levels of glucose transporter proteins, may have a negative impact on important energy and synthetic pathways, as well as protection from free radicals, in immature brain cells. Studies are proposed which examine these changes in gene expression using an in vivo model to delineate regional and cell type differences and using neuronal cultures to further characterize the effect and possible underlying mechanisms, including effects on transcription, message stability, and altered ribonucleoproteins which influence message stability and translation. The long term prospects of this study are that a thorough understanding of the connection between prenatal alcohol exposure and the manifestations of Fetal Alcohol Syndrome will lead to development of effective treatment strategies to minimize or eliminate impairments.