Research Project
3422255
Fetal alcohol syndrome (FAS) is the leading known cause of mental retardation. The biochemical pathway of the teratogenesis is unknown. Recently, a new nonoxidative pathway for alcohol metabolism has been described which conjugates ethanol to free fatty acids via an ethyl ester bond. Our hypothesis is that ethanol crosses the placenta, is metabolized to fatty acid ethyl esters and these products have toxic effects which contribute to alcohol-related teratogenesis. In order to test this model, or any other model of alcohol teratogenesis, we propose to describe the effects of ethanol on the fetal rat brain cell aggregating model. This model undergoes cellular division, biochemical differentiation, and cellular migration of neurons, astrocytes and oligodendrocytes during 40 days in culture. We propose to study the effects of ethanol, both acute and chronic exposure, on these processes. Cellular division and biochemical differentiation will be followed using standard biochemical techniques. Time-dependent variation in the number and geometric distribution of specific neuronal constituent cells will be quantified by computer-assisted analysis using standard image processing techniques. Aggregates will also be studied to determine the ontology and cell specificity of ethanol conjugation to fatty acids. Ethanol treated cultures will be analyzed for fatty acid ethyl esters accumulation and turnover.
