Ethanol as an enhancer of neural differentiation

Ethanol can injure the adult and developing nervous system by disrupting the growth of neural processes. Although many reports emphasize the inhibitory effects of ethanol on process outgrowth, several recent studies indicate that in some brain regions of adult rodents ethanol enhances the development of dendrites (see Messing et al., 1991a for review). In most of these studies, this has been explained as a compensatory response of cells to ethanol-induced loss of neighboring neurons. However little is actually known about the mechanisms involved in enhancement of neurite outgrowth by ethanol. PC12 cells are derived from a rat pheochromocytoma and have been used as a model system to study neural differentiation. They undergo dramatic biochemical and morphological transformation in response to nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), developing a phenotype resembling mature sympathetic neurons (Greene, 1984; Rydel and Greene, 1987). Using PC12 cells to study mechanisms by which ethanol alters neurite outgrowth, we found that ethanol can directly enhance neurite formation by altering signaling pathways distal to the growth factor receptors. Preliminary findings suggest a role for protein kinase C (PKC) in this process.