ETHANOL EXPOSURE AFFECTS GLIAL FIBRILLARY ACIDIC PROTEIN GENE-EXPRESSION AND TRANSCRIPTION DURING RAT-BRAIN DEVELOPMENT

Exposure to ethanol during fetal development reduces the astroglial-sp ecific marker glial fibrillary acidic protein (GFAP) and its mRNA leve ls in brains of fetal rats and in radial glia in primary culture, affe cting the proliferation and differentiation of astrocytes. The objecti ves of this study were to evaluate the possible effect of ethanol on G FAP mRNA levels in astrocytes and to investigate the molecular mechani sm(s) involved in ethanol-induced changes in GFAP expression by analyz ing the GFAP transcription rate, GFAP mRNA stability, and GFAP DNA met hylation. We show here that prenatal exposure to ethanol reduces signi ficantly GFAP immunoreactivity and its mRNA levels in both astrocytes in primary culture and brains of pups from alcohol-fed mothers. Runoff experiments from nuclei of astrocytes indicate that ethanol exposure decreases GFAP transcription rate significantly and reduces GFAP mRNA stability slightly. DNA methylation analysis indicates that prenatal e thanol exposure induces a hypermethylated state of the GFAP DNA in fet al brains. Methylation-mediated repression of GFAP transcription could be a mechanism involved in ethanol-induced reduction of GFAP expressi on. Ethanol-induced alterations in GFAP expression and astroglial deve lopment may underlie the CNS dysfunctions observed after prenatal alco hol exposure.