ALCOHOLS SYNERGIZE WITH NGF TO INDUCE EARLY DIFFERENTIATION OF PC12 CELLS

The role of alcohols in affecting neuromorphogenesis was investigated in a single cell type, pheochromocytoma (PC12). The effect of ethanol at physiological concentrations in this system leads to enhanced morphological and functional differentiation in combination with nerve growth factor (NGF). PC12 cells treated with a suboptimal concentration of NGF (30 ng/ml) and an alcohol (87 mM) underwent rapid morphological differentiation which was dependent upon the side chain length of the alcohol MeOH < EtOH < PrOH < BuOH. Pyrazole at either 5 or 10 mM had no effect on alcohol induced neurite extension. Assessment of the degree of differentiation promoted by the various alcohols was quantified by an increase in neurite extension, a decrease in the incorporation of [H-3]thymidine, an increase in acetylcholine esterase (AChE) activity and immunostaining with neuron specific enolase. Thus, alcohols may function in a specific manner by interacting with transmembrane signalling pathways which promote gene expression and neuronal differentiation.