Document Detail

Binge ethanol-induced neurodegeneration in rat organotypic brain slice cultures: effects of PLA2 inhibitor mepacrine and docosahexaenoic acid (DHA).
MedLine Citation:
PMID:  18592376     Owner:  NLM     Status:  MEDLINE    
Using rat organotypic hippocampal-entorhinal cortical (HEC) slice cultures, we examined whether phospholipase A2 (PLA2) activity is involved in binge alcohol (ethanol)-induced neurodegeneration, and whether docosahexaenoic acid (DHA; 22:6n-3), a fish oil-enriched fatty acid that is anti-inflammatory in brain damage models, is neuroprotective. Assessed with propidium iodide and lactate dehydrogenase (LDH) leakage, neurodamage from ethanol (6 days 100 mM ethanol with four withdrawal periods) was prevented by the PLA2 pan-inhibitor, mepacrine. Also, ethanol-dependent neurodegeneration-particularly in the entorhinal region-was significantly ameliorated by DHA supplementation (25 microM); however, adrenic acid, a 22:4n-6 analog, was ineffective. Consistent with PLA2 activation, [(3)H] liberation was approximately fivefold greater in [(3)H]arachidonic acid-preloaded HEC slice cultures during ethanol withdrawal compared to controls, and DHA supplementation suppressed [(3)H] release to control levels. DHA might antagonize PLA2 activity directly or suppress upstream activators (e.g., oxidative stress); however, other DHA mechanisms could be important in subdueing ethanol-induced PLA2-dependent and independent neuroinflammatory processes.
James Brown; Nicholas Achille; Edward J Neafsey; Michael A Collins
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-01
Journal Detail:
Title:  Neurochemical research     Volume:  34     ISSN:  1573-6903     ISO Abbreviation:  Neurochem. Res.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-26     Completed Date:  2009-03-30     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  260-7     Citation Subset:  IM    
Department of Cell Biology, Neurobiology & Anatomy, Loyola University Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA.
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MeSH Terms
Docosahexaenoic Acids / pharmacology*
Entorhinal Cortex / drug effects*
Enzyme Inhibitors / pharmacology*
Ethanol / administration & dosage*
Hippocampus / drug effects*
Inflammation / prevention & control
Neuroprotective Agents / pharmacology*
Phospholipases A2 / antagonists & inhibitors*
Quinacrine / pharmacology*
Grant Support
R01 AA012034-11/AA/NIAAA NIH HHS; T32 AA013527-09/AA/NIAAA NIH HHS; T32 AA13527/AA/NIAAA NIH HHS
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Neuroprotective Agents; 25167-62-8/Docosahexaenoic Acids; 64-17-5/Ethanol; 83-89-6/Quinacrine; EC A2

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