HIV secreted protein Tat prevents long-term potentiation in the hippocampal CA1 region.

HIV-associated dementia (HAD) is a complication of advanced HIV disease. Both viral products and host cytokines are believed to be involved in the pathogenesis of HIV-associated neurological manifestations. Among the viral products released by HIV-infected cells is the soluble protein Tat. We investigated the effect of exposure of organotypic hippocampal slices to 100 nM recombinant Tat 1-86 on long-term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) at Schaffer collateral/commissural fiber-CA1 synapses. Exposure to Tat 1-86 prevented the induction of LTP without affecting post-tetanic potentiation. Tat 1-72delta31-61, which lacks the neurotoxic domain of Tat, had no significant effect on LTP. Tat's ability to disrupt synaptic plasticity may be relevant to the pathogenesis of the cognitive impairments seen in patients with HIV disease. Copyright 2004 Elsevier B.V.