Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses.
Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses.
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DOI：
10.1093/toxsci/kfs003
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Reiser G
中科院分区：
文献类型：
--
作者：
Haase A;Rott S;Mantion A;Graf P;Plendl J;Thünemann AF;Meier WP;Taubert A;Luch A;Reiser G
在体内，纳米颗粒可以全身分布，然后可能影响次要目标器官，如中枢神经系统（CNS）。迄今为止，对中枢神经系统的推定不良影响很少进行研究。在这里，我们使用主要由神经元和星形胶质细胞以及少量少突胶质细胞组成的混合原代细胞模型来分析表征良好的20和40 nm银纳米颗粒（SNP）的作用。类似的金纳米颗粒作为对照，被证明对所有测试终点都是惰性的。SNP诱导了强烈的大小依赖性细胞毒性。此外，在低浓度范围内（SNP浓度≤10 μg/ml），进一步分化的培养物对SNP处理更敏感。在详细的研究中，我们使用低/中剂量浓度（高达20 μg/ml），发现了强烈的氧化应激反应。随着蛋白质羰基的形成和血红素加氧酶-1的诱导，检测到活性氧（ROS）。我们观察到急性钙反应，明显早于氧化应激反应。抗氧化剂可以减少ROS的形成，但不能减轻钙的反应。最后，我们分别观察了神经元和星形胶质细胞的反应。与神经元相比，星形胶质细胞更容易受到SNP治疗。与此一致的是，SNP主要被星形胶质细胞吸收，而不是被神经元吸收。免疫荧光研究表明混合细胞培养对星形胶质细胞形态有更强的影响。总之，我们可以证明SNP与初级神经细胞中钙失调和ROS形成相关的强大作用，这些作用在中等剂量下已经可以检测到。
In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 μg/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 μg/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosages.
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影响因子：
3.4
作者：
Bowler, Rosemarie M.;Koller, William;Schulz, Paul E.
通讯作者：
Schulz, Paul E.
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：
--
作者：
RICHARDSON, KC;JARETT, L;FINKE, EH
通讯作者：
FINKE, EH
DOI：
10.3389/fneng.2011.00001
发表时间：
2011
期刊：
Frontiers in neuroengineering
影响因子：
--
作者：
Robinette BL;Harrill JA;Mundy WR;Shafer TJ
通讯作者：
Shafer TJ
影响因子：
3.8
作者：
Hussain, Saber M.;Javorina, Amanda K.;Schlager, John J.
通讯作者：
Schlager, John J.