IN-UTERO ETHANOL EXPOSURE RETARDS GROWTH AND ALTERS MORPHOLOGY OF CORTICAL CULTURES - GM1 REVERSES EFFECTS

Ethanol, a developmental neurotoxin, alters plasma membranes' physicoc hemical properties affecting embryogenesis, cell migration, differenti ation, and synaptogenesis. In a previous study using a model for fetal alcohol effects, GM1 ganglioside treatment was shown to reduce ethano l-induced accumulation of endogenous GM1 and fatty acid ethyl esters i n rat fetuses, The present study was initiated to define further the i n utero effects of ethanol and the capacity of GM1 treatment to amelio rate such effects, Wistar darns were exposed to ethanol (intragastrica lly) on gestation day (GD) 7 and GD8 and GD13 and GD14. GM1 gangliosid e (10 mg/kg, im) was given 24 hr before ethanol administration, Cortic al cultures were derived from GD15 and GD20 fetuses, GM1, which is hig hly localized on the cellular plasma membrane outer surface of CNS cel ls, was used as a marker molecule to assess cell integrity, Cholera to xin/antitoxin/fluorescence immunohistochemistry was used to localize G M1. Results indicate that the brief in utero exposure to ethanol affec ted cell growth and morphology, A marked retardation of cell developme nt and arborization was observed as early as 24 hr after plating, Etha nol-exposed cells evidenced considerably altered GM1 localization. Suc h alterations likely reflect losses of membrane integrity, These in ut ero ethanol-induced pathologies are remarkably diminished in cultures derived from ethanol-exposed fetuses of dams treated with GM1.