title: Ethanol promotes neuronal apoptosis by inhibiting phosphatidylserine accumulation.
abstract: Prenatal and postnatal ethanol exposure induces abnormal cell death in the nervous system. We have previously reported that docosahexaenoic acid (DHA; 22:6n-3) prevents neuronal apoptosis through promoting phosphatidylserine (PS) accumulation. Previously, we have shown in C6 glioma cells that ethanol inhibits the accumulation of PS caused by DHA supplementation. In this report, we demonstrate that in vitro or in vivo exposure to ethanol inhibits DHA-dependent PS accumulation and neuronal survival. We found that Neuro 2A cells exposed to ethanol accumulated considerably less PS in response to the DHA enrichment and were less effective at phosphorylating Akt and suppressing caspase-3 activity under serum-starved or staurosporine-treated conditions. The in vivo paradigm correlated well with the in vitro findings. We found that the total PS and DHA contents in the fetal hippocampus were slightly but significantly lowered by the prenatal ethanol exposure. Fetal hippocampal cultures obtained at embryonic day 18 from ethanol-treated pregnant rats contained significantly higher apoptotic cells after 7 days in vitro under basal conditions and exhibited particular susceptibility to cell death induced by trophic factor removal in comparison with the pair-fed control group. The reduction of PS and the resulting neuronal cell death inappropriately enhanced during development may contribute to the defects in brain function often observed in fetal alcohol syndrome.
authors.affiliation: Section of Mass Spectrometry, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH, Bethesda, Maryland.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akbar
authors.forename: Joseph
authors.initials: J
authors.lastname: Baick
authors.forename: Frances
authors.initials: F
authors.lastname: Calderon
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wen
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D000431:Ethanol / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D010718:Phosphatidylserines / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D005227:Fatty Acids; D010718:Phosphatidylserines; D004281:Docosahexaenoic Acids; D000431:Ethanol; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases