Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network.
Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network.
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DOI：
10.1080/17435390.2018.1425497
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发表时间：
2018-03
期刊：
影响因子：
5
通讯作者：
Hong Y
中科院分区：
文献类型：
--
作者：
Repar N;Li H;Aguilar JS;Li QQ;Drobne D;Hong Y
银纳米颗粒（AgNP）是最广泛使用的纳米颗粒之一，并且存在于各种产品中。这种普遍性导致在日常生活中不可避免地接触到这些颗粒。然而，银纳米颗粒对神经元和星形胶质细胞网络的影响在很大程度上仍然是未知的。在这项研究中，我们使用来自人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被的银纳米颗粒（AgSC）诱导的神经毒性。分别用星形胶质细胞和神经元标记物胶质细胞酸性蛋白和微管相关蛋白2（MAP 2）进行免疫染色，结果显示，暴露于0.1 µg/mL浓度的AgSC增加了星形胶质细胞/神经元的比例。相反，较高浓度的AgSC（5.0 µg/ml）显著改变了星形胶质细胞的形态。这些结果表明，星形胶质细胞对AgSC暴露敏感，低浓度的AgSC促进星形胶质细胞发生。此外，我们的研究结果表明，银干细胞减少神经突起的生长，减少突触后密度蛋白95和突触素的表达，并诱导神经退行性变的浓度依赖性方式。我们的研究结果还表明，MAP 2亚型的表达和磷酸化状态，调节Akt/糖原合成酶激酶-3/半胱天冬酶-3信号通路的激活，可能发挥重要作用，银SC介导的神经毒性。我们还发现，AgNO 3暴露仅轻微减少神经突起的生长，并对MAP 2的表达几乎没有影响，这表明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AgSC和抗氧化剂抗坏血酸共同处理时，这些作用中的大多数都降低了，这意味着氧化应激是AgSC介导的星形胶质细胞/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。
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.
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影响因子：
10.2
作者：
Hsiao IL;Bierkandt FS;Reichardt P;Luch A;Huang YJ;Jakubowski N;Tentschert J;Haase A
通讯作者：
Haase A
影响因子：
4.7
作者：
Chen, YM;Vartiainen, NE;Swanson, RA
通讯作者：
Swanson, RA
DOI：
10.1093/toxsci/kfs003
发表时间：
2012-04
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Haase A;Rott S;Mantion A;Graf P;Plendl J;Thünemann AF;Meier WP;Taubert A;Luch A;Reiser G
通讯作者：
Reiser G
影响因子：
2.1
作者：
Ji, Jun Ho;Jung, Jae Hee;Yu, Il Je
通讯作者：
Yu, Il Je
影响因子：
3.5
作者：
Arora, S.;Jain, J.;Paknikar, K. M.
通讯作者：
Paknikar, K. M.