Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellargranule cells

The neuropathology of the effects of ethanol on the developing central nerv ous system are similar to those of patients with mutations in L1, a neural cell adhesion molecule. This observation suggests that inhibition of L1 pla ys a role in the pathogenesis of alcohol-related neurodevelopmental disorde rs. Here we examine the effects of ethanol on L1 hemophilic binding and on L1 mediated neurite outgrowth. Ethanol had no effect on cell adhesion or ag gregation in a myeloma cell line expressing full-length human L1. In contra st, the rate of L1-mediated neurite outgrowth of rat postnatal day 6 cerebe llar granule cells grown on a substratum of Ng-CAM, the chick homologue of L1, was inhibited by 48.6% in the presence of ethanol with a half-maximal c oncentration of 4.7 mM, The same effect was found with soluble L1-Fc, thus showing that the inhibitory effect is not dependent on cell adhesion. In co ntrast, neither laminin nor N-cadherin-mediated neurite outgrowth was inhib ited by physiologic concentrations of ethanol. We conclude that one mechani sm of ethanol's toxicity to the developing central nervous system may be th e inhibition of L1-mediated neurite outgrowth.