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Monday, April 27, 2009

Ethanol inhibition of aspartyl-asparaginyl-β-hydroxylase in fetal alcohol spectrum disorder: Potential link to the impairments in central nervous system neuronal migration
Alcohol Volume 43, Issue 3, May 2009, Pages 225-240
Chronic gestational exposure to ethanol caused dose-dependent impairments in neuronal migration and corresponding reductions in AAH protein expression in developing cerebella.
In addition, prenatal ethanol exposure inhibited insulin and IGF-I–stimulated directional motility in isolated cerebellar granule neurons. Ethanol-treated neuronal cultures (50 mM × 96 h) also had reduced levels of AAH protein. Mechanistically, we showed that AAH protein could be phosphorylated on Ser residues by GSK-3β, and that chemical inhibition of GSK-3β and/or global Caspases increases AAH protein in both control- and ethanol-exposed cells.
Ethanol-impaired neuronal migration in FASD is associated with reduced AAH expression. Because ethanol increases the activities of both GSK-3β and Caspases, the inhibitory effect of ethanol on neuronal migration could be mediated by increased GSK-3β phosphorylation and Caspase degradation of AAH protein.
Request Reprint E-Mail: Suzanne_DeLaMonte_MD@Brown.edu
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