Muscle-derived factors reverse the cholinotoxic effects of ethanol during early neuroembryogenesis in the chick embryo

Abstract

The interaction between muscle-derived factors and ethanol on cholinergic neuronal expression was studied in the chick embryo during early neuroembryogenesis using choline acetyltransferase (ChAT) as cholinergic neuronal marker. Ethanol (10 mg/50 μl) and limb muscle extract (130 μg protein/50 μl) (LME) were administered in ovo either alone or concomitantly at embryonic days 1–3 (E1–E3); or ethanol was given E1–E3 and followed by LME at E4–E7. All groups were sacrificed at embryonic day 8 (E8) and ChAT activity was assayed in homogenates of whole brain and of spinal cord. As previously reported 6,8,31, ethanol at E1–3 produced a 30% decrease in brain ChAT activity and 35% in spinal cord. Concomitant administration of ethanol and LME at embryonic days E1–E3 eliminated the decrease in choline acetyltransferase activity produced by ethanol in the brain, but not in the spinal cord. On the other hand, administration of LME at embryonic days E4–E7 to embryos pretreated with ethanol at embryonic days E1–E3, raised ChAT activity to control level in the spinal cord, but only partially restored ChAT activity in the brain. In view of the alleged neurotrophic effects of muscle-derived factors on neuronal survival and neuronal growth, we interpret these findings to suggest that LME in addition to its ability to decrease natural neuronal death, may prevent death resulting from neurotoxicity.