Ethanol inhibits development of dendrites and synapses in rat hippocampal pyramidal neuron cultures

Evidence suggests that some neuropathologic manifestations of Fetal Alcohol Syndrome (FAS) result from the disruption of neuromorphogenesis and synapse formation in the hippocampus. Prior research in this laboratory has shown that ethanol in the medium during the first 24 h in culture increases the number of minor processes (the precursors of axons and dendrites) and accelerates the rate at which axons are formed in low-density cultures of embryonic rat hippocampal neurons. The current study examined the effects of ethanol on the subsequent development of dendrites and synapses in these cultures. Quantitative morphometric analysis utilized double-immunofluorescent staining for MAP2 and synapsin I to visualize dendrites and synaptic specializations, respectively. Six days of ethanol (200, 400 or 600 mg/dl) in the medium, beginning at the time of plating, resulted in decreases in total dendritic length per cell, dendrite number per cell, length of individual dendrites and synapse number per innervated dendrite but had no effect on cell survival. The decrease in synapse number was correlated with dendrite length, suggesting that ethanol's effects on synapse number are secondary to its effects on dendritogenesis. Taken together with our previous findings, these results are the first to demonstrate that ethanol has differential effects on axonal and dendritic growth in a culture model of neurons that are vulnerable to ethanol-induced cytoarchitectural abnormalities during development in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.