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

<p>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.</p

Normalized expression data for the NASC Arabidopsis developmental series (Additional file ) were extracted and plotted as shown

The set of genes listed in Table 1 were split into three groups; the grouping was done according to historical views of the polyadenylation complex. Thus, genes encoding CPSF and CSTF subunits are shown in the top panel, PAPS and PABN genes in the middle, and the remaining genes in the lower panel. This grouping also applies for the plots shown in Figures 3–5. The legends indicate the correspondence between the plots and the respective Arabidopsis gene identification designation. The numerical key for each array experiment is given along the X-axis. The full list of the keys can be found in the Additional file . Here is a brief description of these samples, including wt and some mutants: 1–7, root 7–21 days; 8–10, stem 7–21 days; 11–27, leaf 7–35 days; 28–38, whole plant 7–23 days; 39–49, shoot apex 7–21 days; 50–71, flowers and floral organs 21+ day; 72–79, 8 week seeds and siliques. The arrows point to the positions for mature pollen.<p><b>Copyright information:</b></p><p>Taken from "Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling"</p><p>http://www.biomedcentral.com/1471-2164/9/220</p><p>BMC Genomics 2008;9():220-220.</p><p>Published online 14 May 2008</p><p>PMCID:PMC2391170.</p><p></p

Normalized expression data for the NASC Arabidopsis abiotic stress series (Additional file ) were extracted and plotted as shown

The legends indicate the correspondence between the plots and the respective Arabidopsis gene identification designation. The numerical key for each array experiment is given along the X-axis and the detail can be found in Additional file . Here is a brief list of the stress treatments: 1–18, control; 19–30, cold; 31–42, osmotic; 43–54, salt; 55–68, drought; 69–80, genotoxic; 81–92, oxidative; 93–106, UV-B; 107–120, wound; 121–136, heat; 137–141, cell culture control; 142–149, cell culture + heat.<p><b>Copyright information:</b></p><p>Taken from "Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling"</p><p>http://www.biomedcentral.com/1471-2164/9/220</p><p>BMC Genomics 2008;9():220-220.</p><p>Published online 14 May 2008</p><p>PMCID:PMC2391170.</p><p></p

Normalized expression data for the NASC Arabidopsis biotic stress series (Additional file ) were extracted and plotted as shown

The legends indicate the correspondence between the plots and the respective Arabidopsis gene identification designation. The numerical key for each array experiment is given along the X-axis. While the full list of the agents can be found in Additional file , here is a brief list: 1–16, control and infection; 17–22, control and infection; 23–36, control and elicitors treatment; 37–52, dark and different light treatment.<p><b>Copyright information:</b></p><p>Taken from "Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling"</p><p>http://www.biomedcentral.com/1471-2164/9/220</p><p>BMC Genomics 2008;9():220-220.</p><p>Published online 14 May 2008</p><p>PMCID:PMC2391170.</p><p></p

Normalized expression data for the NASC Arabidopsis chemical/hormone series (Additional file ) were extracted and plotted as shown

The legends indicate the correspondence between the plots and the respective Arabidopsis gene identification designation. The numerical key for each array experiment is given along the X-axis, and the detail can be found in Additional file . The single arrows indicate the position for cycloheximide; double arrows for GA mutants; empty arrows for imbibition and ABA treatment.<p><b>Copyright information:</b></p><p>Taken from "Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling"</p><p>http://www.biomedcentral.com/1471-2164/9/220</p><p>BMC Genomics 2008;9():220-220.</p><p>Published online 14 May 2008</p><p>PMCID:PMC2391170.</p><p></p

The values for each gene in the array analysis of mature pollen were plotted as shown

<p><b>Copyright information:</b></p><p>Taken from "Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling"</p><p>http://www.biomedcentral.com/1471-2164/9/220</p><p>BMC Genomics 2008;9():220-220.</p><p>Published online 14 May 2008</p><p>PMCID:PMC2391170.</p><p></p