Evaluation of HIV-1 Tat induced neurotoxicity in rat cortical cell culture

In a substantial number of cases, Human Immunodeficiency Virus type 1 (HIV- 1) infection causes neuronal cell loss and leads to the development of AIDS associated dementia. Several studies have suggested that both host and vir al factors contribute to neuronal loss. Here we studied the effect of HIV-1 Tat in primary rat neuronal cells as a model to understand mechanism of ne uronal cell death. At nano molar concentration, recombinant Tat induced cel l death in primary rat mixed cortical neurons. Tat could also induce uptake of calcium in primary rat cultures. When cells were incubated with NMDA re ceptor antagonists, MK-801 and D-CPP, cell death and Ca-45 uptake were inhi bited. Under similar conditions non-NMDA antagonists, NBQX, DNQX and CNQX, and sodium channel antagonist, TTX, did not inhibit Tat induced neuronal ce ll death. In a similar way HIV associated products from in vitro HIV-1 infe cted cells induced neuronal cell death which was inhibited by NMDA receptor antagonist. Results presented in this paper suggest that activation of NMD A receptors by HIV-1 Tat is responsible for neuronal cell death in primary rat cortical neurons.