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 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.

[1]  L. J. Chandler,et al.  Ethanol inhibits NMDA receptor-mediated excitotoxicity in rat primary neuronal cultures. , 1993, Alcoholism, clinical and experimental research.

[2]  G. Fein,et al.  Effect of chronic alcohol abuse on the CNS morbidity of HIV disease. , 1998, Alcoholism, clinical and experimental research.

[3]  L. Mucke,et al.  Transgenic models in the study of AIDS dementia complex. , 1996, Current topics in microbiology and immunology.

[4]  B. Tabakoff Alcohol and AIDS--is the relationship all in our heads? , 1994, Alcoholism, clinical and experimental research.

[5]  O. Meucci,et al.  gp120-Induced Neurotoxicity in Hippocampal Pyramidal Neuron Cultures: Protective Action of TGF-β1 , 1996, The Journal of Neuroscience.

[6]  E. Korpi,et al.  Ethanol inhibits NMDA-induced toxicity and trophism in cultured cerebellar granule cells. , 1995, Acta physiologica Scandinavica.

[7]  E. Neafsey,et al.  Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema‐based mechanism , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  S. Lipton Neuronal injury associated with HIV-1: approaches to treatment. , 1998, Annual review of pharmacology and toxicology.

[9]  L. Pulliam,et al.  The HIV envelope protein gp120 is toxic to human brain‐cell cultures through the induction of interleukin‐6 and tumor necrosis factor‐&agr; , 1995, AIDS.

[10]  B. Kristensen,et al.  Markers for neuronal degeneration in organotypic slice cultures. , 1999, Brain research. Brain research protocols.

[11]  S. Zakhari Molecular mechanisms underlying alcohol-induced cardioprotection: contribution of hemostatic components. Introduction to the symposium. , 1999, Alcoholism, clinical and experimental research.