Growth factors attenuate the cholinotoxic effects of ethanol during early neuroembryogenesis in the chick embryo

The interaction between growth factors and ethanol on cholinergic neuronal expression was studied in the chick embryo during early neuroembryogenesis using choline acetyltransferase activity as a cholinergic marker. As we have previously reported (Brodie & Vernadakis, Dev. Brain Res. 56: 223-228, 1990; Kentroti and Vernadakis, Dev. Brain Res. 56: 205-210, 1990), ethanol administration in ovo at embryonic days 1-3 produced a 30% decrease in choline acetyltransferase activity. Nerve growth factor and epidermal growth factor administration alone, at embryonic days 1-3, produced a slight increase in choline acetyltransferase activity of both brain and spinal cord when examined at embryonic day 8. Concomitant administration of either nerve growth factor or epidermal growth factor with ethanol eliminated the decrease in choline acetyltransferase activity produced by ethanol. Moreover, administration of either nerve growth factor or epidermal growth factor at embryonic days 4-7 to embryos pretreated with ethanol at days 1-3 raised choline acetyltransferase activity to a level similar to that observed in controls. Thus the growth factors reversed the ethanol-induced cholinergic insult and restored the cholinergic population to normal. These findings provide evidence of a possible role of NGF and EGF in interfering with the neurotoxic effects of ethanol during embryogenesis.