Inhibition of Ethanol Neurotoxicity by Treatment with Growth Factors and Estrogen

Abstract

Ethanol ingestion by pregnant women is the primary cause of fetal alcohol syndrome, which is characterized by brain abnormalities and decreased mental capacity. In the present study, cultured neurons from embryonic rat cortices were used to study the effects of ethanol on cell survival and the potential for neuroprotection by certain growth factors and estrogen. Neurons were grown in the presence of a glial plane and in the absence of serum. Survival was assessed following chronic treatment with ethanol (45 mM) in the presence and absence of either nerve growth factor (NGF, 100ng/ml), basic fibroblast growth factor (bFGF, 5ng/ml), insulin-like growth factor I or II (IGF-I, IGF-II, both 10ng/ml), or estrogen (Es, 10nM) added on days one and four in vitro. On day in vitro 4 (DIV4) ethanol effects on neuronal viability were significantly prevented by NGF, bFGF, IGF-I, and Es. DIV6 survival of ethanol-treated neurons was increased significantly by treatment with NGF, bFGF, IGF-I, IGF-II, and Es. Nerve growth factor, bFGF, and IGF-I effects were shown to be dose-dependent. Administration of 1-100 ng/ml NGF, 0.05-5 ng/ml bFGF and 0.1-10ng/ml IGF-I led to statistically significant effects at 10, 5, and 1 ng/ml, respectively. Thus, ethanol’s effect on neuronal survival may be inhibited by simultaneous treatment with physiological doses of these factors.

Keywords

• ethanol neurotoxicity
• growth factors
• estrogen