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 20nm 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 0.1μg/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 α/β at Tyr216and Tau at Ser396and 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.
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Aynun N
AN
Begum
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Jose S
JS
Aguilar
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Lourdes
L
Elias
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA. Electronic address: yhong@westernu.edu.
Yiling
Y
Hong
D002118:Calcium; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053768:Metal Nanoparticles; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012834:Silver / Q000494:pharmacology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D005971:Glutamates; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D050598:Vesicular Glutamate Transport Protein 1; C002744:3-nitrotyrosine; D012834:Silver; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; D052248:Nitric Oxide Synthase Type I; D002118:Calcium
Glutamatergic neurons; Human embryonic stem cells; Neurodegeneration; Neurodifferentiation; Neurotoxicity; Silver nanoparticle