Ethanol alters astrocyte development: A study of critical periods using primary cultures

Using astrocytes obtained from 21-day-old rat fetuses, in primary culture, we have analyzed the effect of prenatal alcohol consumption on DNA and protein synthesis of astrocytes during their development. The variation in sensitivity of astrocytes to ethanol in vitro during the proliferation and maturation periods was also assessed. Control astrocytes showed peaks of DNA and protein synthesis at 8 and 15 days, respectively. A significant decrease in both DNA and protein synthesis was found in astrocytes from fetuses prenatally exposed to ethanol. This effect on DNA synthesis was also observed when control astrocytes were exposed to ethanol (100mM) in vitro during the entire culture period. The effects on astrocytes of short term (48h) exposure to ethanol during the proliferation or differentiation periods on the above mentioned parameters and on the cell cycle as well as the possible recovery from these effects were also evaluated. Decreases in DNA and protein synthesis were found in both periods. However, DNA synthesis and content were more affected in astrocytes exposed to ethanol during the proliferation period. This effect correlates with an accumulation of cells in the G_o/G₁ phase of the cell cycle. On the other hand, when cells exposed to ethanol were cultured in alcohol-free medium to assess recovery, only cells exposed to ethanol during days 4 to 6 still showed DNA ethanol-induced effects at 21 days. In conclusion, our results show that ethanol consumption during gestation induces serious damage to cortical astrocyte progenitor cells. Our results further demonstrate that although astrocytes are more sensitive to the toxic effect of alcohol during the proliferation period, exposure to ethanol during glial maturation also alters their normal development.