PERTURBATION OF TARGET-DIRECTED NEURITE OUTGROWTH IN EMBRYONIC CNS COCULTURES GROWN IN THE PRESENCE OF ETHANOL

Studies were conducted to determine the influence of ethanol on target -directed fiber outgrowth in culture, using embryonic chick spinal cor d-muscle, and fetal rat septal-hippocampal co-cultured explants. Proce ss extension from the spinal cord and septal explants in control cultu res was selectively oriented toward the appropriate target tissue. Eth anol in the culture medium (500 mg/dl) eliminated this target-oriented outgrowth in both systems, although the overall extent of neurite out growth was not affected. In an effort to further characterize the sour ce of this disruption, target explants were grown alone, with and with out ethanol, and the target-conditioned culture media was subsequently harvested and placed on newly plated spinal cord or septal explants, to determine whether ethanol decreased the target production of solubl e substances. To determine whether deposition of substrate-bound mater ials by the target tissue was affected by ethanol, spinal cord or sept al explants were plated in wells which had previously been occupied by the appropriate target tissue. These studies revealed that ethanol si gnificantly inhibited production of soluble and substrate-bound materi als by muscle explants, but not by hippocampal explants. It was conclu ded that the ethanol-induced loss of target-directed neurite outgrowth in the spinal cord explants could be accounted for primarily by the a ttenuated production of neurotrophic/neurotropic substances by the mus cle tissue. The loss of target-directionality in the septal explants a ppeared to be due to other factors, possibly related to ethanol-induce d compromise of the capacity of the septal neurons to respond appropri ately to target-derived neurotrophic/neurotropic substances. The impli cations of these results for the fetal alcohol syndrome are considered .