Ethanol exerts different effects on myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase expression in differentiating CG-4 oligodendrocytes.
Evidence suggests that abnormal myelination is one factor contributing to the neuoropathology associated with fetal alcohol syndrome. We investigated the potential teratogenic effects of ethanol (EtOH) on myelin formation by determining its effects on the developmentally regulated increased expression of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in differentiating CG-4 oligodendrocytes (OLGs). By using CG-4 OLGs in vitro we identified processes altered by ethanol actions exerted directly on OLGs. During the first 8 days of development, EtOH decreased the expression of the major structural 18.5 and 14 kDa MBP isoforms by at least 40% at 4 days of development. EtOH concentrations between 25 and 75 mM inhibited MBP expression in a dose-dependent manner. Adding or withdrawing EtOH on specific days of differentiation reversibly modulated the expression of MBP, and the degree of inhibition was directly related to the length of ethanol exposure. As little as two consecutive days of EtOH exposure either early or late during development caused at least a 20% inhibition, however, no short critical time window of EtOH vulnerability for the inhibition was observed. The ethanol effect was selective for MBP expression, as EtOH did not alter the developmentally-regulated increased expression of CNP isozymes or enzyme activity. The results indicate that one factor contributing to the development of fetal alcohol syndrome may be defective myelination resulting from delayed and decreased MBP expression.
Bichenkov
E
E
Department of Pathology, Anatomy, and Cell Biology, Medical College of Thomas Jefferson University, 269 Jefferson Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107, USA.
Ellingson
J S
JS
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D010727:Phosphoric Diester Hydrolases; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D004676:Myelin Basic Protein; D020033:Protein Isoforms; D000431:Ethanol; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase