Alcohol inhibits neurite extension and increases N-myc and c-myc proteins

Alcohol teratogenesis may be due, in part, to inhibition of neuronal differentiation by alcohol. Because decreases in the N-myc and c-myc proteins are believed to be linked causally to neuronal differentiation, we hypothesized that alcohol would increase N-myc and c-myc proteins in undifferentiated neuronal cells and would oppose the decreases in these two proteins that normally precede differentiation. In undifferentiated LA-N-5 cultured human neuroblastoma cells, alcohol increased N-myc protein levels (178% vs. control cells) and c-myc levels (222% of control). Retinoic acid decreased N-myc and c-myc and induced neurite outgrowth (a differentiation marker). Alcohol prevented retinoic acid-elicited decreases in both myc isoforms and prevented neurite outgrowth. A significant 100% increase in c-myc and an upward trend (48%) in N-myc were observed in CA1 pyramidal neurons of the dorsal hippocampus in mouse fetuses exposed prenatally to alcohol. These data suggest that increases in N-myc and c-myc protein levels are associated with inhibition of neurite extension by alcohol.