Ethanol Inhibits L1-mediated Neurite Outgrowth in Postnatal Rat Cerebellar Granule Cells*

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.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-05-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.274.19.13264PMID 10224086PMCID PMC4197854
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells.

  1999cited by this paper
• A Neuronal Form of the Cell Adhesion Molecule L1 Contains a Tyrosine-Based Signal Required for Sorting to the Axonal Growth Cone

  1998cited by this paper
• Nervous System Defects of AnkyrinB (−/−) Mice Suggest Functional Overlap between the Cell Adhesion Molecule L1 and 440-kD AnkyrinB in Premyelinated Axons

  1998cited by this paper
• A conserved role for L1 as a transmembrane link between neuronal adhesion and membrane cytoskeleton assembly.

  1998cited by this paper
• Characterization of Ethanol‐Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1

  1998cited by this paper
• The Neural Cell Adhesion Molecule L1 Interacts with the AP-2 Adaptor and Is Endocytosed via the Clathrin-Mediated Pathway

  1998cited by this paper
• Ethanol Does Not Inhibit the Adhesive Activity ofDrosophila Neuroglian or Human L1 in DrosophilaS2 Tissue Culture Cells*

  1997cited by this paper
• Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome.

  1997cited by this paper
• Cellular and molecular neuroscience of alcoholism.

  1997cited by this paper
• NCAM140 Interacts with the Focal Adhesion Kinase p125fak and the SRC-related Tyrosine Kinase p59fyn*

  1997cited by this paper
• Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin

  1997cited by this paper
• Cell migration: a physically integrated molecular process.

  1996cited by this paper
• CAM-FGF Receptor Interactions: A Model for Axonal Growth

  1996cited by this paper
• Fetal alcohol syndrome : diagnosis, epidemiology, prevention, and treatment

  1996cited by this paper
• DIRECTIONAL NEURITE OUTGROWTH AND AXONAL DIFFERENTIATION OF EMBRYONIC HIPPOCAMPAL NEURONS ARE PROMOTED BY A NEURITE OUTGROWTH DOMAIN OF THE B2‐CHAIN OF LAMININ

  1996cited by this paper
• Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation

  1996cited by this paper
• Deficiency of essential neurotrophic factors in conditioned media produced by ethanol-exposed cortical astrocytes.

  1996cited by this paper
• Casein Kinase II Phosphorylates the Neural Cell Adhesion Molecule L1

  1996cited by this paper
• CAM-FGF receptor interactions: a model for axonal growth.

  1996cited by this paper
• Alcohol inhibits cell-cell adhesion mediated by human L1 [published erratum appears in J Cell Biol 1996 Jun;133(5):1139-40]

  1996cited by this paper
• Involvement of p90rsk in Neurite Outgrowth Mediated by the Cell Adhesion Molecule L1*

  1996cited by this paper
• The cytoplasmic domain of the cell adhesion molecule L1 is not required for homophilic adhesion.

  1995cited by this paper
• Growth cones are actively influenced by substrate-bound adhesion molecules

  1995cited by this paper
• Pattern of Malformation in Offspring of Chronic Alcoholic Mothers

  1995cited by this paper
• FGF inhibits neurite outgrowth over monolayers of astrocytes and fibroblasts expressing transfected cell adhesion molecules.

  1995cited by this paper
• Overexpression of ε-Protein Kinase C Enhances Nerve Growth Factor-induced Phosphorylation of Mitogen-activated Protein Kinases and Neurite Outgrowth (*)

  1995cited by this paper
• Ethanol enhances growth factor activation of mitogen-activated protein kinases by a protein kinase C-dependent mechanism.

  1995cited by this paper
• Perturbation of target-directed neurite outgrowth in embryonic CNS co-cultures grown in the presence of ethanol.

  1995cited by this paper
• Ethanol attenuation of ganglioside sialylation and neuritogenesis.

  1994cited by this paper
• The Production of Arachidonic Acid Can Account for Calcium Channel Activation in the Second Messenger Pathway Underlying Neurite Outgrowth Stimulated by NCAM, N‐Cadherin, and L1

  1994cited by this paper
• Characterisation of the second messenger pathway underlying neurite outgrowth stimulated by FGF.

  1994cited by this paper
• Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.

  1994cited by this paper
• Responsiveness of cultured septal and hippocampal neurons to ethanol and neurotrophic substances

  1994cited by this paper
• Ethanol inhibits neural cell-cell adhesion.

  1994cited by this paper
• Developmental cues modulate GABAA receptor subunit mRNA expression in cultured cerebellar granule neurons

  1993cited by this paper
• Ethanol enhances neurite outgrowth in primary cultures of rat cerebellar macroneurons.

  1993cited by this paper
• Calcium influx into neurons can solely account for cell contact- dependent neurite outgrowth stimulated by transfected L1

  1992cited by this paper
• Functional expression of a full-length cDNA coding for rat neural cell adhesion molecule L1 mediates homophilic intercellular adhesion and migration of cerebellar neurons.

  1992cited by this paper
• Molecular structure and functional testing of human L1CAM: an interspecies comparison.

  1991cited by this paper
• Chronic ethanol exposure increases levels of protein kinase C δ and ε and protein kinase C-mediated phosphorylation in cultured neural cells

  1991cited by this paper
• A revised conservative estimate of the incidence of FAS and its economic impact.

  1991cited by this paper
• Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells.

  1991cited by this paper
• Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells.

  1991cited by this paper
• Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels.

  1991cited by this paper
• Sensitive competitive‐binding elisas for quantifying free kappa and lambda light chains in cerebrospinal fluid

  1991cited by this paper
• Ethanol enhances growth factor-induced neurite formation in PC12 cells.

  1991cited by this paper
• Ethanol inhibits NMDA-stimulated neurite growth by sensory neurons in vitro.

  1990cited by this paper
• Specific effects of ethanol on neurite-promoting proteoglycans of neuronal origin.

  1990cited by this paper
• L1-mediated axon outgrowth occurs via a homophilic binding mechanism.

  1989cited by this paper
• Immunocytochemical and electrophysiological differentiation of rat cerebellar granule cells in explant cultures

  1987cited by this paper
• An L1-like molecule, the 8D9 antigen, is a potent substrate for neurite extension.

  1987cited by this paper
• The appearance of an L1-like molecule in the chick primary visual pathway

  1986cited by this paper
• Biosynthesis and membrane topography of the neural cell adhesion molecule L1.

  1985cited by this paper
• Ethanol neurotoxicity: effects on neurite formation and neurotrophic factor production in vitro.

  1985cited by this paper
• L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum

  1983cited by this paper
• The fetal alcohol syndrome.

  1978cited by this paper
• The fetal alcohol syndrome.

  1978cited by this paper
• In vitro behavior of granule cells from staggerer and weaver mutants of mice

  1977cited by this paper
• The maintenance and identification of mouse cerebellar granule cells in monolayer culture.

  1977cited by this paper
• Pattern of malformation in offspring of chronic alcoholic mothers.

  1973cited by this paper

• Choline supplementation mitigates effects of bilirubin in cerebellar granule neurons in vitro

  2024cites this paper
• Neuronal miR-17-5p contributes to interhemispheric cortical connectivity defects induced by prenatal alcohol exposure

  2023cites this paper
• In vitro biomarkers of developmental neurotoxicity

  2022cites this paper
• Maternal Ethanol Exposure Acutely Elevates Src Family Kinase Activity in the Fetal Cortex

  2021cites this paper
• Altering Cell-Cell Interaction in Prenatal Alcohol Exposure Models: Insight on Cell-Adhesion Molecules During Brain Development

  2021cites this paper
• Bilirubin inhibits lipid raft dependent functions of L1 cell adhesion molecule in rat pup cerebellar granule neurons

  2020cites this paper
• Choline ameliorates ethanol induced alterations in tyrosine phosphorylation and distribution in detergent-resistant membrane microdomains of L1 cell adhesion molecule in vivo.

  2020cites this paper
• Analysis of Drosophila nervous system development following an early, brief exposure to ethanol

  2019cites this paper
• Alcohol Cell Death

  2018cites this paper
• Developmental Neurotoxicity of Alcohol: Effects and Mechanisms of Ethanol on the Developing Brain

  2018cites this paper
• L1 coupling to ankyrin and the spectrin‐actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis

  2018cites this paper
• Cell Adhesion Molecules as Targets of Developmental Toxicants

  2018cites this paper
• In Vitro Biomarkers of Developmental Neurotoxicity

  2017cites this paper
• Ethanol (E) Impairs Fetal Brain GSH Homeostasis by Inhibiting Excitatory Amino-Acid Carrier 1 (EAAC1)-Mediated Cysteine Transport

  2017cites this paper
• Developmental alcohol exposure leads to a persistent change on astrocyte secretome

  2016cites this paper
• Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation

  2016cites this paper
• Roles of Stress-related Factors in Embryonic Neurogenesis

  2016cites this paper
• TOLUENE DISRUPTION OF THE FUNCTIONS OF L1 CELL ADHESION MOLECULE AT CONCENTRATIONS ASSOCIATED WITH OCCUPATIONAL EXPOSURES

  2016influential citation
• The Effects of Alcohol Exposure on Fetal Development

  2016cites this paper
• Choline Ameliorates Deficits in Balance Caused by Acute Neonatal Ethanol Exposure

  2015cites this paper
• Fetal Alcohol Spectrum Disorders

  2015cites this paper
• Choline partially prevents the impact of ethanol on the lipid raft dependent functions of l1 cell adhesion molecule.

  2014cites this paper
• Effect of Lipid Raft Disruption on Ethanol Inhibition of L1 Adhesion

  2014cites this paper
• Arylsulfatase B modulates neurite outgrowth via astrocyte chondroitin‐4‐sulfate: Dysregulation by ethanol

  2014cites this paper
• Prenatal ve postnatal alkol kullanımı sonucunda rat beyinlerinde oluşan nörodejenerasyonun betain ve/veya omega-3 uygulanmasıyla önlenmesinin araştırılması

  2014cites this paper
• Chronic prenatal ethanol exposure produces neurobehavioural and metabolic dysfunction in guinea pig offspring

  2014cites this paper
• Chlorhexidine inhibits L1 cell adhesion molecule–mediated neurite outgrowth in vitro

  2014cites this paper
• Neurotrophic Factors and Ethanol Neurotoxicity

  2014cites this paper
• How Mary Ellen Avery Influenced my Career as an Investigator

  2014cites this paper
• Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes.

  2014cites this paper
• Mitogen-activated protein kinase modulates ethanol inhibition of cell adhesion mediated by the L1 neural cell adhesion molecule

  2013cites this paper
• Neuropathological review of 138 cases genetically tested for X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases

  2013cites this paper
• Understanding variability in ethanol teratogenicity

  2013cites this paper
• Inhibition of cholinergic muscarinic signaling by ethanol: Potential mechanism of developmental neurotoxicity and biological plausibility for the beneficial effects of choline supplementation

  2013cites this paper
• L1 cell adhesion molecule signaling is inhibited by ethanol in vivo.

  2013cites this paper
• Titanium and iron in lung of a soldier with nonspecific interstitial pneumonitis and bronchiolitis after returning from Iraq.

  2012cites this paper
• Ethanol affects differentiation-related pathways and suppresses Wnt signaling protein expression in human neural stem cells.

  2012cites this paper
• Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus

  2012cites this paper
• Retracted: Ethanol disrupts axon outgrowth stimulated by netrin‐1, GDNF, and L1 by blocking their convergent activation of Src family kinase signaling

  2012cites this paper
• Effects of ethanol exposure on nervous system development in zebrafish.

  2012cites this paper
• Chapter 19 – In vitro biomarkers of developmental neurotoxicity

  2011cites this paper
• Effects of Ethanol and NAP on Cerebellar Expression of the Neural Cell Adhesion Molecule L1

  2011cites this paper
• Ethanol alters BDNF-induced Rho GTPase activation in axonal growth cones.

  2011cites this paper
• Signal Transduction and Neurotoxicity: What Can We Learn from Experimental Culture Systems?

  2011cites this paper
• L1 cell adhesion molecule promotes resistance to alcohol-induced silencing of growth cone responses to guidance cues.

  2011cites this paper
• siRNA‐mediated GABAB receptor at early fetal rat brain upon acute and chronic ethanol exposure: Down regulation of PKA and p‐CREB expression

  2011cites this paper
• Central Axonal Development and Pathology in Early Life

  2011cites this paper
• Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts

  2011cites this paper
• Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal slices: Role of astrocytes and extracellular matrix proteins.

  2011cites this paper
• Two Alcohol Binding Residues Interact across a Domain Interface of the L1 Neural Cell Adhesion Molecule and Regulate Cell Adhesion*

  2011cites this paper
• Alcoholism and Alternative Splicing of Candidate Genes

  2010cites this paper
• L1CAM malfunction in the nervous system and human carcinomas

  2010cites this paper
• Cell Signaling and Neurotoxicity

  2010cites this paper
• Quantitative assessment of neurite outgrowth in human embryonic stem cell-derived hN2 cells using automated high-content image analysis.

  2010cites this paper
• Inhibition of cerebellar granule cell turning by alcohol.

  2010cites this paper
• Ethanol inhibits neuritogenesis induced by astrocyte muscarinic receptors

  2010influential citation
• Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells.

  2010cites this paper
• Alcohol and Cell Death

  2010cites this paper
• Metals and Cell Adhesion

  2010cites this paper
• Ethanol inhibits muscarinic receptor-induced axonal growth in rat hippocampal neurons.

  2009influential citation
• Impact of Ethanol on the Developing GABAergic System

  2009cites this paper
• Ethanol inhibits L1 cell adhesion molecule tyrosine phosphorylation and dephosphorylation and activation of pp60src

  2009cites this paper
• The Activation of M1 Muscarinic Receptor Signaling Induces Neuronal Differentiation in Pyramidal Hippocampal Neurons

  2009cites this paper
• Developmental neurotoxicity testing in vitro: models for assessing chemical effects on neurite outgrowth.

  2008cites this paper
• Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol‐induced apoptosis

  2008cites this paper
• Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease

  2008cites this paper
• Ethanol increases fetal human neurosphere size and alters adhesion molecule gene expression.

  2008cites this paper
• An alcohol binding site on the neural cell adhesion molecule L1

  2008cites this paper
• NeuroRhythmics: software for analyzing time-series measurements of saltatory movements in neuronal processes.

  2008cites this paper
• Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.

  2008cites this paper
• Effects of ethanol on axon outgrowth and branching in developing rat cortical neurons.

  2008influential citation
• Neural stem cell transplantation in a model of fetal alcohol effects.

  2007cites this paper
• L1 cell adhesion molecule is neuroprotective of alcohol induced cell death.

  2007cites this paper
• ERK-dependent and -independent pathways trigger human neural progenitor cell migration.

  2007cites this paper
• Therapeutic effects of aniracetam on cognitive deficits induced by ethanol teratogenicity: A novel treatment approach through synaptic AMPA receptor modulation

  2007cites this paper
• Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome

  2007influential citation
• Transforming growth factor β1 and ethanol affect transcription and translation of genes and proteins for cell adhesion molecules in B104 neuroblastoma cells

  2006cites this paper
• Reversal of Neuronal Migration in a Mouse Model of Fetal Alcohol Syndrome by Controlling Second-Messenger Signalings

  2006cites this paper
• L1 cell adhesion molecule found in human CSF varies as a function of age.

  2006cites this paper
• Elevated phenylalanine levels interfere with neurite outgrowth stimulated by the neuronal cell adhesion molecule L1 in vitro

  2006cites this paper
• ReversalofNeuronalMigrationinaMouseModelof FetalAlcoholSyndromebyControlling Second-MessengerSignalings

  2006cites this paper
• Signaling pathways regulating cell motility: a role in ethanol teratogenicity?

  2006cites this paper
• Glycosylation is altered by ethanol in rat hippocampal cultured neurons.

  2006cites this paper
• Ethanol inhibits L1 cell adhesion molecule activation of mitogen‐activated protein kinases

  2006cites this paper
• Alcohol Teratogenesis: Mechanisms of Damage and Strategies for Intervention

  2005cites this paper
• Ethanol perturbs the secretory pathway in astrocytes.

  2005cites this paper
• Reversal of ethanol toxicity in embryonic neurons with growth factors and estrogen.

  2005cites this paper
• Synergistic effects of the peptide fragment D-NAPVSIPQ on ethanol inhibition of synaptic plasticity and NMDA receptors in rat hippocampus.

  2005cites this paper
• Ethanol inhibits brain-derived neurotrophic factor-mediated intracellular signaling and activator protein-1 activation in cerebellar granule neurons.

  2004cites this paper
• Ethanol induces heterotopias in organotypic cultures of rat cerebral cortex.

  2004cites this paper
• Ethanol Antagonist Peptides: Structural Specificity without Stereospecificity

  2004cites this paper
• Brain development in mice lacking L1–L1 homophilic adhesion

  2004cites this paper
• Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1‐stimulated neurite outgrowth of cerebellar granule neurons

  2004influential citation
• Human neural stem cells are more sensitive than astrocytes to ethanol exposure.

  2003cites this paper
• Selective vulnerability of cerebellar granule neuroblasts and their progeny to drugs with abuse liability

  2003cites this paper
• Time-lapse analysis of ethanol's effects on axon growth in vitro.

  2003cites this paper
• Alcohol and the Developing Brain: Neuroanatomical Studies

  2003cites this paper
• Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans.

  2003cites this paper
• Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases.

  2003cites this paper
• Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity

  2003cites this paper