EFFECTS OF RETINOIC ACID ON NB-69 HUMAN NEUROBLASTOMA-CELLS AND FETAL-RAT MID-BRAIN NEURONS

Retinoids are chemical compounds which play important roles in ontogen etic development and cranio-caudal differentiation in animals, but the ir effect on phenotypic expression of neurotransmitters are unknown. W e studied the pharmacological and morphological effects of retinoic ac id (RA) on two types of immature vertebrate neurons, the human derived neuroblastoma cells, NB69, and fetal rat mid brain neurons in culture . The pharmacological effects of RA on the cultures and their relation to catecholamine and acetylcholine neurotransmission were evaluated a ccording the levels of catecholamines, tyrosine hydroxylase (TH) activ ity, TH immunostaining, and choline acetyltransferase (CAT) activity, respectively. RA reduces catecholamine levels and TH activity in NB69 cells and the number of dopamine neurons in cultures derived from rat fetal mid brain. The detrimental effect of RA on mid brain neurons is dose- dependent; limited to TH+ cells at low concentrations (100 to 50 0 nM) and toxic for all types of cells at high concentrations (1 to 2 mu M). RA increases CAT activity in NB 69 cells and produces phenotypi c differentiation of these to a more mature neuronal phenotype with mo re prolonged neurite extensions. Therefore, RA may play a trophic posi tive role in the differentiation of immature cells to cholinergic neur ons; this contrasts with the detrimental effects of RA on catecholamin e neurons.