REVERSAL OF ALCOHOLS EFFECTS ON NEURITE EXTENSION AND ON NEURONAL GAP43 B50, N-MYC, AND C-MYC PROTEIN-LEVELS BY RETINOIC ACID/

Alcohol teratogenesis may be due in part to inhibition of neuronal dif ferentiation by ethanol. We showed previously that alcohol decreased n euronal differentiation (neurite extension) and increased N-myc and c- myc neuronal protein levels. Since Growth-Associated Protein 43 (GAP43 /B50) levels must increase for neurons to differentiate, alcohol may d ecrease GAP43/B50. Alcohol dose-dependently (0-0.5%) decreased GAP43/B 50 protein levels by up to 92% in immature LA-N-5 cells. Five nM retin oic acid alone induced differentiation and increased GAP43/B50 levels to 230% of control. These retinoic acid-induced increases in GAP43/B50 and neurite outgrowth, and decreases in N-myc and c-myc, were reverse d dose,dependently by alcohol (0-0.5%). Conversely, the adverse effect s of 0.25% alcohol on neurite extension, GAP43/B50, N-myc, and c-myc w ere prevented by 15 and 45 nM retinoic acid. These results suggest tha t inhibition of neuronal differentiation by alcohol and prevention of such effects by retinoic acid are related to changes in GAP43/B50, N-m yc and c-myc.