HIV-1 gp120 neurotoxicity in brain cultures is prevented by moderate ethanol pretreatment

The HIV-1 coat protein gp120, a potent neurotoxin that may underlie AIDS de mentia, activates glia to cause neurotoxicity via the NMDA receptor and per haps other routes. We find that pretreating cultures of rat organotypic cor tical/hippocampal slices or cerebellar granule cells subchronically with et hanol in physiological concentrations (20-30 mM; 6 days) largely or even co mpletely inhibits neurodegeneration due to gp120. However, NMDA-induced neu rotoxicity appears unaffected by moderate ethanol pretreatment, indicating that ethanol's neuroprotection against gp120 is upstream of the NMDA recept or, possibly at a glial activation stage. The results could lead to a bette r understanding of relationships between ethanol, glia and neurodegeneratio n, particularly in AIDS. NeuroReport 11:1219-1222 (C) 2000 Lippincott Willi ams & Wilkins.