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Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network
Nanotoxicology ( IF 3.6 ) Pub Date : 2018-01-15 , DOI: 10.1080/17435390.2018.1425497
Neza Repar 1, 2 , Hao Li 3, 4 , Jose S. Aguilar 1 , Qingshun Quinn Li 3, 4 , Damjana Drobne 2 , Yiling Hong 1, 3
Affiliation  

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.

中文翻译:

银纳米颗粒在人类胚胎干细胞衍生的神经元和星形胶质细胞网络中诱导神经毒性

银纳米颗粒(AgNPs)是使用最广泛的纳米颗粒之一,存在于多种产品中。这种普遍存在导致在日常生活中不可避免地暴露于这些颗粒。但是,AgNPs对神经元和星形胶质细胞网络的影响仍然是未知之数。在这项研究中,我们使用源自人类胚胎干细胞的神经元和星形胶质细胞作为细胞模型来研究柠檬酸盐包覆的AgNPs(AgSCs)诱导的神经毒性。星形胶质纤维酸性蛋白和微管相关蛋白2(MAP2)分别通过星形胶质细胞和神经元标记进行免疫染色,结果表明暴露于0.1 µg / mL的AgSCs会增加星形胶质细胞/神经元比率。相反,较高浓度的AgSCs(5.0 µg / ml)会显着改变星形胶质细胞的形态。这些结果表明,星形胶质细胞对暴露于AgSC敏感,而低浓度的AgSCs促进星形胶质细胞生成。此外,我们的结果表明,AgSCs减少了神经突的生长,降低了突触后密度蛋白95和突触素的表达,并以浓度依赖的方式诱导了神经变性。我们的发现还表明,由Akt /糖原合酶激酶-3 / caspase-3信号通路的激活调节的MAP2亚型的表达和磷酸化状态可能在AgSC介导的神经毒性中起重要作用。我们还发现AgNO 降低突触后密度蛋白95和突触素的表达,并以浓度依赖的方式诱导神经退行性变。我们的发现还表明,由Akt /糖原合酶激酶-3 / caspase-3信号通路的激活调节的MAP2亚型的表达和磷酸化状态可能在AgSC介导的神经毒性中起重要作用。我们还发现AgNO 降低突触后密度蛋白95和突触素的表达,并以浓度依赖的方式诱导神经退行性变。我们的发现还表明,由Akt /糖原合酶激酶-3 / caspase-3信号通路的激活调节的MAP2亚型的表达和磷酸化状态可能在AgSC介导的神经毒性中起重要作用。我们还发现AgNO3次暴露仅略微减少了神经突向外生长,并且对MAP2表达几乎没有影响,表明AgSCs和AgNO 3具有不同的神经元毒性机制。此外,当细胞培养物与AgSCs和抗氧化剂抗坏血酸共同处理时,大多数这些作用都降低了,这表明氧化应激是AgSC介导的星形胶质/神经元毒性的主要原因,并且抗氧化剂可能具有神经保护作用。 。
更新日期:2018-02-13
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