7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:101 (abstract no. M.A.1038)
Tiziana S, Levi G; Instituto Superiore di Sanita, Laboratory of Pathophysiology, Roma, Italy

OBJECTIVE: It has been suggested that neural cell damage frequently observed in AIDS patients may be partly related to the neurotoxicity of HIV-coded products, such as the envelope protein gp120. Picomolar concentrations of gp120 cause neuronal death in various non-human neural cell culture systems, and this death has been interpreted as due to competition with neurotrophic factors, to increased calcium influx through voltage-gated calcium channels, or to interaction with the N-methyl-D-aspartate subtype of glutamate receptors. The aim of the present study was to determine whether acute exposure to gp120 could potentiate the neurotoxic action of glutamate on a defined population of purified neurons. METHODS AND RESULTS: Cultures highly enriched (95%) in granule neurons were prepared from 8-day postnatal rat cerebella. After 7-8 days of incubation the cells were exposed for 15 min either to a buffered Locke's solution (controls) or to the same solution supplemented with: i) 1 or 100 pM recombinant gp120 (Genentech, S; Francisco); ii) 0.05 mM glutamate, with or without 1 mM APV (an NMDA receptor antagonist); iii) 0.05 mM glutamate and 1 or 100 pM gp120. After culturing for another 24 h in their original culture medium, total granule cells and dead granule cells (which bind the fluorochrome propidium iodide) were counted. In controls, dead cells accounted for 4-7% of total. Exposure to gp120 did not alter this proportion, while glutamate caused a 1.5-2 fold increase in the number of dead neurons, which was reversed by APV. In the case of simultaneous exposure to glutamate and gp120 the neuronal cell death was 30-300% greater than that caused by glutamate alone.

CONCLUSIONS: Since exposure to 1 or 100 pM gp120 did not induce an increase in the release of endogenous glutamate from the cells, these observations suggest that low concentrations of gp120 can potentiate the excitotoxic of glutamate on cultured rat cerebellar granule neurons.

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