Neurochemical Research

, Volume 34, Issue 2, pp 260–267

Binge Ethanol-induced Neurodegeneration in Rat Organotypic Brain Slice Cultures: Effects of PLA2 Inhibitor Mepacrine and Docosahexaenoic Acid (DHA)

  • James BrownIII
  • Nicholas Achille
  • Edward J. Neafsey
  • Michael A. Collins
Original Paper

DOI: 10.1007/s11064-008-9765-y

Cite this article as:
Brown, J., Achille, N., Neafsey, E.J. et al. Neurochem Res (2009) 34: 260. doi:10.1007/s11064-008-9765-y

Abstract

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 μM); however, adrenic acid, a 22:4n-6 analog, was ineffective. Consistent with PLA2 activation, [3H] liberation was approximately fivefold greater in [3H]arachidonic acid-preloaded HEC slice cultures during ethanol withdrawal compared to controls, and DHA supplementation suppressed [3H] 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.

Keywords

AlcoholWithdrawalHippocampusEntorhinal cortexPhospholipase A2Arachidonic acidNeuroprotection

Abbreviations

AA

Arachidonic acid

ADA

Adrenic acid

DHA

Docosahexaenoic acid

HEC

Hippocampal-entorhinal cortical

MEP

Mepacrine

PKB

Protein kinase B

PLA2

Phospholipase A2

PS

Phosphatidylserine

ROS

Reactive oxygen species

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • James BrownIII
    • 1
  • Nicholas Achille
    • 1
  • Edward J. Neafsey
    • 1
  • Michael A. Collins
    • 1
  1. 1.Department of Cell Biology, Neurobiology & AnatomyLoyola University Stritch School of MedicineMaywoodUSA