HIV-I gpI20 neurotoxicity in brain cultures is prevented by moderate ethanol pretreatment.
The HIV-1 coat protein gp 20, a potent neurotoxin that may underlie AIDS dementia, activates glia to cause neurotoxicity via the NMDA receptor and perhaps other routes. We find that pretreating cultures of rat organotypic cortical/hippocampal slices or cerebellar granule cells subchronically with ethanol in physiological concentrations (20-30 mM; 6 days) largely or even completely inhibits neurodegeneration due to gp120. However, NMDA-induced neurotoxicity appears unaffected by moderate ethanol pretreatment, indicating that ethanol's neuroprotection against gp120 is upstream of the NMDA receptor, possibly at a glial activation stage. The results could lead to a better understanding of relationships between ethanol, glia and neurodegeneration, particularly in AIDS.
Collins
M A
MA
Department of Molecular and Cellular Biochemistry, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Neafsey
E J
EJ
Zou
J Y
JY
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018728:Entorhinal Cortex / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000187:drug effects* / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000633:toxicity
D017077:Culture Media, Conditioned; D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000431:Ethanol; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase