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.
Division of Biochemistry, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA.
Abdelhak
A
Belmadani
Sripathirathan
S
Kumar
Matthew
M
Schipma
Michael A
MA
Collins
Edward J
EJ
Neafsey
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