Silver nanoparticles exhibit coating and dose-dependent neurotoxicity in glutamatergic neurons derived from human embryonic stem cells

Silver nanoparticles (AgNPs) are used extensively as anti-microbial agents in various products, but little is known about their potential neurotoxic effects. In this study, we used glutamatergic neurons derived from human embryonic stem cells as a cellular model to study 20 nm citrate-coated AgNPs (AgSCs) and Polyvinylpyrrolidone-coated AgNPs (AgSPs) induced neurotoxicity. AgSCs significantly damaged neurite outgrowths; increased the production of reactive oxygen species and Ca2+ influxes; reduced the expression of MAP2, PSD95, vGlut1 and NMDA receptor proteins at concentrations as low as 0.1 mu g/ml. In contrast, AgSPs exhibited neurotoxicity only at higher concentration. Furthermore, our results showed that AgSCs induced glutamate excitotoxicity by the activation of calmodulin and the induction of nitric oxide synthase; increased the phosphorylation of glycogen synthase kinase-3 alpha/beta at Tyr(216) and Tau at Ser(396) and reduced the expression of Tau46, which are typically observed in Alzheimer's disease. This study indicated that stem cells can provide an excellent platform for studying nanoparticle induced neurotoxicity. Published by Elsevier B.V.