title: Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells.
abstract: The neuropathology of the effects of ethanol on the developing central nervous system are similar to those of patients with mutations in L1, a neural cell adhesion molecule. This observation suggests that inhibition of L1 plays a role in the pathogenesis of alcohol-related neurodevelopmental disorders. Here we examine the effects of ethanol on L1 homophilic binding and on L1-mediated neurite outgrowth. Ethanol had no effect on cell adhesion or aggregation in a myeloma cell line expressing full-length human L1. In contrast, the rate of L1-mediated neurite outgrowth of rat postnatal day 6 cerebellar granule cells grown on a substratum of NgCAM, the chick homologue of L1, was inhibited by 48.6% in the presence of ethanol with a half-maximal concentration 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 contrast, neither laminin nor N-cadherin-mediated neurite outgrowth was inhibited by physiologic concentrations of ethanol. We conclude that one mechanism of ethanol's toxicity to the developing central nervous system may be the inhibition of L1-mediated neurite outgrowth.
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. cfb3@po.cwru.edu
authors.forename: C F
authors.initials: CF
authors.lastname: Bearer
authors.forename: A R
authors.initials: AR
authors.lastname: Swick
authors.forename: M A
authors.initials: MA
authors.lastname: O'Riordan
authors.forename: G
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D000431:Ethanol