ETHANOL NEUROTOXICITY ON NEUROBLAST-ENRICHED CULTURES FROM 3-DAY-OLD CHICK-EMBRYO IS ATTENUATED BY THE NEURONOTROPHIC ACTION OF GABA

In the present study, using neuroblast:enriched cultures derived from three-day-old chick embryos (E3WE), we examined the morphological effe cts of ethanol and/or GABA, as well as the developmental profile of th e cholinergic and GABAergic neuronal phenotypes, as assessed by the ac tivities of choline acetyltranferase (ChAT) and glutamate decarboxylas e (GAD). Cultures exposed to ethanol (50 mM) exhibited smaller and few er aggregates than controls with a neuritic network that lacked fascic ulation. In cultures treated with GABA (10(-5) M) alone or ethanol+GAB A the size and number of the neuronal aggregates was increased and als o neuritic arborization and fasciculation was enhanced. Thus, addition of GABA restored the normal growth pattern in the ethanol-treated cul tures. As previously shown, E3WE culture treated with ethanol alone sh owed a decrease in both ChAT and GAD activities compared to controls. Both cholinergic and GABAergic neuronal phenotypes were enhanced in cu ltures treated with GABA as assessed by increases in ChAT and GAD acti vities, respectively, compared to controls. Moreover, in cultures trea ted concomitantly with ethanol and GABA both ChAT and GAD activities w ere higher than in ethanol-alone-treated cultures. Thus, the presence of GABA in the ethanol-treated cultures counteracted the decline in Ch AT and GAD activities observed in the ethanol-alone-treated cultures. We conclude that GABA through its neuronotrophic actions can rescue ne uroblasts from ethanol insult and restore neuronal phenotypes.