In utero ethanol exposure retards growth and alters morphology of cortical cultures: GM1 reverses effects.
Ethanol, a developmental neurotoxin, alters plasma membranes' physicochemical properties affecting embryogenesis, cell migration, differentiation, and synaptogenesis. In a previous study using a model for fetal alcohol effects, GM1 ganglioside treatment was shown to reduce ethanol-induced accumulation of endogenous GM1 and fatty acid ethyl esters in rat fetuses. The present study was initiated to define further the in utero effects of ethanol and the capacity of GM1 treatment to ameliorate such effects. Wistar dams were exposed to ethanol (intragastrically) on gestation day (GD) 7 and GD8 and GD13 and GD14. GM1 ganglioside (10 mg/kg, im) was given 24 hr before ethanol administration. Cortical cultures were derived from GD15 and GD20 fetuses. GM1, which is highly localized on the cellular plasma membrane outer surface of CNS cells, was used as a marker molecule to assess cell integrity. Cholera toxin/antitoxin/fluorescence immunohistochemistry was used to localize GM1. Results indicate that the brief in utero exposure to ethanol affected cell growth and morphology. A marked retardation of cell development and arborization was observed as early as 24 hr after plating. Ethanol-exposed cells evidenced considerably altered GM1 localization. Such alterations likely reflect losses of membrane integrity. These in utero ethanol-induced pathologies are remarkably diminished in cultures derived from ethanol-exposed fetuses of dams treated with GM1.
Laev
H
H
Division of Neuroscience, New York State Psychiatric Institute, NY 10032, USA.
Karpiak
S E
SE
Gokhale
V S
VS
Hungund
B L
BL
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D046508:Culture Techniques; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005865:Gestational Age; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar
D005677:G(M1) Ganglioside