ALCOHOL, ASTROGLIA, AND BRAIN-DEVELOPMENT

Glial cells constitute one of the most common cell types in the brain. They play critical roles in central nervous system (CNS) development. Recent evidence demonstrates that glial cells are profoundly affected by prenatal alcohol exposure, suggesting that alterations in these ce lls may participate in CNS abnormalities associated with ethanol-induc ed teratogenesis. In vivo studies show that prenatal exposure to alcoh ol hampers myelinogenesis and is associated with neuroglial heterotopi as and abnormal astrogliogenesis. Studies using primary cultures of ra t cortical astrocytes show that ethanol affects DNA, RNA, and protein synthesis, decreases the number of mitotic cells, alters the content a nd distribution of several cytoskeletal proteins including the astrogl ial marker, glial fibrillary acidic protein (GFAP), and the levels of plasma-membrane glycoproteins, reduces the capacity of astrocytes to s ecrete growth factors, and induces oxidative stress. Furthermore, etha nol exposure during early embryogenesis alters the normal development of radial glia cells (the main astrocytic precursors), delays the onse t of GFAP expression, and decreases mRNA GFAP levels in fetal and post natal brains and in radial glia and astrocytes in primary culture. Rec ent evidence suggests that ethanol interferes with the transcription p rocess of GFAP, thus leading to a reduction in GFAP-gene expression du ring astrogliogenesis. However, brief exposure of rats to high levels of ethanol during the neonatal period (the period of astrocyte differe ntiation) causes a transient gliosis, with an increase in GFAP and its mRNA levels. These findings indicate that astroglial cells are an imp ortant target of ethanol toxicity during central nervous system (CNS) development.