Effects of Silver Nanoparticles on Primary Mixed Neural Cell Cultures: Uptake, Oxidative Stress and Acute Calcium Responses
Autor: | Stephanie Rott, Andreas Taubert, Andreas Luch, Johanna Plendl, Andrea Haase, Georg Reiser, Andreas F. Thünemann, Alexandre Mantion, Wolfgang Meier, P. Graf |
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Rok vydání: | 2012 |
Předmět: |
silver nanoparticles
Silver Central nervous system Metal Nanoparticles neurons chemistry.chemical_element Calcium Biology Toxicology medicine.disease_cause Silver nanoparticle Microscopy Electron Transmission medicine Animals oxidative stress Nanotoxicology Cytotoxicity Cells Cultured protein carbonyls Calcium metabolism chemistry.chemical_classification Reactive oxygen species calcium Molecular biology Rats medicine.anatomical_structure chemistry Institut für Chemie Reactive Oxygen Species 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit Oxidative stress Astrocyte |
Zdroj: | Toxicological Sciences |
ISSN: | 1096-0929 1096-6080 |
DOI: | 10.1093/toxsci/kfs003 |
Popis: | 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 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. |
Databáze: | OpenAIRE |
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