Effect of ethanol and docosahexaenoic acid on nerve growth factor-induced neurite formation and neuron specific growth-associated protein gene expression in PC12 cells.

It is known that prenatal and postnatal exposure to ethanol can result in hyperactive behavior and learning disturbance in offspring. We have previously shown that docosahexaenoic acid (DHA) ameliorated hyperactivity induced by in utero ethanol exposure in rat pups. The present study is designed to clarify the effects of DHA on neurite outgrowth and gene expression of GAP-43 and SCG10, neuron specific growth-associated proteins (GAPs) in PC12 cells treated with ethanol. Ethanol seemed to enhance the neurite outgrowth induced by nerve growth factor (NGF). DHA administration further increased neurite outgrowth in both NGF alone and the combination of NGF and ethanol treated PC12 cells. DHA treatment increased the levels of both GAP-43 and SCG10 mRNAs, and simultaneous administration of ethanol suppressed the elevation of GAP-43 and SCG10 mRNA enhanced by DHA. The present study has demonstrated, for the first time, the effect of ethanol and DHA on GAPs' gene expression. Interaction of ethanol and docosahexaenoic acid in NGF-induced neurite formation, as well as the mechanisms by which DHA ameliorate the hyperactivity induced by in utero ethanol exposure, are to be elucidated.