Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network

Abstract

Silver nanoparticles (AgNPs) are among the most extensively used nanoparticles and are found in a variety of products. This ubiquity leads to inevitable exposure to these particles in everyday life. However, the effects of AgNPs on neuron and astrocyte networks are still largely unknown. In this study, we used neurons and astrocytes derived from human embryonic stem cells as a cellular model to study the neurotoxicity that is induced by citrate-coated AgNPs (AgSCs). Immunostaining with the astrocyte and neuron markers, glial fibrillary acidic protein and microtubule-associated protein 2 (MAP2), respectively, showed that exposure to AgSCs at the concentration of 0.1 µg/mL increased the astrocyte/neuron ratio. In contrast, a higher concentration of AgSCs (5.0 µg/ml) significantly changed the morphology of astrocytes. These results suggest that astrocytes are sensitive to AgSC exposure and that low concentrations of AgSCs promote astrogenesis. Furthermore, our results showed that AgSCs reduced neurite outgrowth, decreased the expression of postsynaptic density protein 95 and synaptophysin, and induced neurodegeneration in a concentration-dependent manner. Our findings additionally suggest that the expression and phosphorylation status of MAP2 isoforms, as modulated by the activation of the Akt/glycogen synthase kinase-3/caspase-3 signaling pathway, may play an important role in AgSC-mediated neurotoxicity. We also found that AgNO3 exposure only slightly reduced neurite outgrowth and had little effect on MAP2 expression, suggesting that AgSCs and AgNO3 have different neuronal toxicity mechanisms. In addition, most of these effects were reduced when the cell culture was co-treated with AgSCs and the antioxidant ascorbic acid, which implies that oxidative stress is the major cause of AgSC-mediated astrocytic/neuronal toxicity and that antioxidants may have a neuroprotective effect.

An Experimental Investigation of Ultraweak Photon Emission from Adult Murine Neural Stem Cells

“…For example, Kaur and Tikoo 59 reported that the cytotoxicity effect of AgNPs depended on dose, surface potential of nanoparticles, and cells type in skin epithelial A431, lung epithelial A549 and murine macrophages RAW264.7 cells. Repar et al 60 examined the neurotoxicity induced by citrate-coated AgNPs (AgSCs) in neurons and astrocytes originated from human embryonic stem cells. When neurons and astrocytes were exposed to 0.1 μg/mL of AgSCs the astrocyte/neuron ratio is increased and helped astrogenesis, but 5.0 μg/mL of AgSCs significantly changed the morphology of astrocytes.…”

Evaluating the cytotoxicity of graphene oxide using embryonic stem cells‐derived cells

“…However, they suffer from low tissue availability and unrepresentative cellular responses, respectively. A number of recent studies have therefore used human ESC‐derived neural cell models to explore the toxicity of nanoparticles and have demonstrated that stem cells provide an excellent platform for studying the cytotoxicity of nanomaterials (Begum, Aguilar, Elias, & Hong, ; Oh et al, ; Repar et al, ). We were therefore motivated to test the utility of ESC‐derived RPE cells to evaluate the cytotoxicity of GO nanosheets and to compare their responses to two commonly used models: primary hRPEs and ARPE19 cell lines.…”

3D Printed Neural Regeneration Devices

“…However, more information is needed about the toxicity of the conductive inks used in the neural regeneration system, including threshold limits, safe doses, and biocompatibility. For instance, although nanoscale silver particles are now in widespread use in a variety of commercial products, these particles can cause neurotoxicity, reduced neurite outgrowth, inflammation and oxidative stress . Alternative approaches using noncontact stimuli such as light, magnetic fields, or ultrasound could be promising alternatives for neural stimulation devices …”