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 cord-muscle, and fetal rat septal-hippocampal co-cultured explants. Process extension from the spinal cord and septal explants in control cultures was selectively oriented toward the appropriate target tissue. Ethanol in the culture medium (500 mg/dl) eliminated this target-oriented outgrowth in both systems, although the overall extent of neurite outgrowth was not affected. In an effort to further characterize the source of this disruption, target explants were grown alone, with and without 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 soluble substances. To determine whether deposition of substrate-bound materials by the target tissue was affected by ethanol, spinal cord or septal explants were plated in wells which had previously been occupied by the appropriate target tissue. These studies revealed that ethanol significantly inhibited production of soluble and substrate-bound materials by muscle explants, but not by hippocampal explants. It was concluded that the ethanol-induced loss of target-directed neurite outgrowth in the spinal cord explants could be accounted for primarily by the attenuated production of neurotrophic/neurotropic substances by the muscle tissue. The loss of target-directionality in the septal explants appeared to be due to other factors, possibly related to ethanol-induced compromise of the capacity of the septal neurons to respond appropriately to target-derived neurotrophic/neurotropic substances. The implications of these results for the fetal alcohol syndrome are considered.