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Effects of silver nanoparticles on primary mixed neural cell cultures: Uptake, oxidative stress and acute calcium responses

  • 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 mu g/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 mu g/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 stressIn 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 mu g/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 mu g/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.show moreshow less

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Author details:Andrea Haase, Stephanie Rott, Alexandre Mantion, Philipp Graf, Johanna Plendl, Andreas F. ThünemannORCiD, Wolfgang P. Meier, Andreas TaubertORCiDGND, Andreas Luch, Georg Reiser
DOI:https://doi.org/10.1093/toxsci/kfs003
ISSN:1096-6080
Title of parent work (English):Toxicological sciences
Publisher:Oxford Univ. Press
Place of publishing:Oxford
Publication type:Article
Language:English
Year of first publication:2012
Publication year:2012
Release date:2017/03/26
Tag:calcium; neurons; oxidative stress; protein carbonyls; silver nanoparticles
Volume:126
Issue:2
Number of pages:12
First page:457
Last Page:468
Funding institution:Federal Land Sachsen Anhalt (CBBS) [C1]; Federal Ministry of Food, Agriculture and Consumer Protection (BMELV); Federal Institute for Risk Assessment (BfR); Federal Institute for Materials Research and Testing (BAM); Swiss National Science Foundation; NCCR-Nanosciences; Free University; University of Potsdam; MPI of Colloids and Interfaces; Adolf-Martens e.V.
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie
Peer review:Referiert
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