There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Infection by lentiviruses such as human immunodeficiency virus (HIV) and Maedi-Visna
virus (MVV) is associated with neurodegenerative disorders. We have investigated the
neurotoxic mechanisms of a synthetic peptide of transactivating protein tat of MVV
in striatal neuronal cultures. Tat peptide (but not control peptide) caused neuronal
death, without affecting glial viability, in a time- and dose-dependent manner. Significant
neuronal death was not observed until 6-8 h after tat peptide application (2.35-2350
nM), whereas half maximal and maximal cell death was observed after 12 and 24 h respectively.
Tat peptide neurotoxicity could be partially inhibited by blockade of either N-methyl-D-aspartate
(NMDA)- or non-NMDA receptors, suggesting that excessive neuroexcitation by glutamate
or its analogues may contribute to tat-neurotoxicity. Furthermore, when both these
glutamate receptor subtypes were blocked simultaneously, an increased degree of neuroprotection
was observed. Finally, tat peptide toxicity was also reduced by blockade of L-type
calcium channels. Calcium imaging revealed that intracellular calcium increases slowly
upon tat application, predominantly due to entry of extracellular calcium. These results
indicate that cellular calcium entry through voltage-gated calcium channels following
activation of both NMDA and non-NMDA receptors, and subsequent accumulation of intracellular
calcium may contribute to the neuronal death induced by tat protein.