Effects of Silver Nanoparticles on Primary Mixed Neural Cell Cultures: Uptake, Oxidative Stress and Acute Calcium Responses
Open Access
- 12 January 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 126 (2), 457-468
- https://doi.org/10.1093/toxsci/kfs003
Abstract
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.Keywords
This publication has 40 references indexed in Scilit:
- The inhibitory effects of nano‐Ag on voltage‐gated potassium currents of hippocampal CA1 neuronsEnvironmental Toxicology and Water Quality, 2011
- In Vitro Assessment of Developmental Neurotoxicity: Use of Microelectrode Arrays to Measure Functional Changes in Neuronal Network Ontogeny1Frontiers in Neuroengineering, 2011
- Nanoparticles Induce Changes of the Electrical Activity of Neuronal Networks on Microelectrode Array NeurochipsEnvironmental Health Perspectives, 2010
- Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticlesToxicology Letters, 2009
- Unique Cellular Interaction of Silver Nanoparticles: Size-Dependent Generation of Reactive Oxygen SpeciesThe Journal of Physical Chemistry B, 2008
- A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress–mediated mitochondrial injuryNeuroscience, 2008
- Activation of protease‐activated receptors in astrocytes evokes a novel neuroprotective pathway through release of chemokines of the growth‐regulated oncogene/cytokine‐induced neutrophil chemoattractant familyEuropean Journal of Neuroscience, 2007
- Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s diseaseNeuroscience, 2007
- Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: Effect of lipopolysaccharideToxicology, 2006
- U‐Shaped dose‐response curves: Their occurrence and implications for risk assessmentJournal of Toxicology and Environmental Health, 1990