Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning.
Consumers of moderate amounts of ethanol have a lower risk of Alzheimer's dementia than do abstainers. In Alzheimer's disease the brain contains many extracellular plaques composed of amyloid-beta (Abeta), a neurotoxic protein linked to pathogenesis of the disease. Here we report that moderate ethanol preconditioning (20-30 mM for 6 days) of organotypic hippocampal-entorhinal slice cultures prevents Abeta-induced neurotoxicity and apoptosis as measured by media lactate dehydrogenase levels and staining with propidium iodide and Hoechst 33342. With Abeta, as with our previous studies of the neurotoxic HIV-1 protein gp120, moderate ethanol preconditioning may interfere with various glial-mediated neurotoxic responses in the slices to Abeta. In addition, we found that moderate ethanol preconditioning causes an almost 3-fold increase in brain levels of heat shock protein 70 (hsp70), a protective molecular chaperone. Our results suggest possible molecular mechanisms underlying the protective effect of moderate drinking against Alzheimer's dementia.
Belmadani
Abdelhak
A
Division of Biochemistry, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA.
Kumar
Sripathirathan
S
Schipma
Matthew
M
Collins
Michael A
MA
Neafsey
Edward J
EJ
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002492:Central Nervous System Depressants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000494:pharmacology* / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D006836:Hydro-Lyases / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D011419:Propidium; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D002492:Central Nervous System Depressants; D018840:HSP70 Heat-Shock Proteins; D011419:Propidium; D000431:Ethanol; D006836:Hydro-Lyases; C045581:lactate dehydratase; C017807:bisbenzimide ethoxide trihydrochloride