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    Effects of silver nanoparticles on primary mixed neural cell cultures:
    uptake, oxidative stress and acute calcium responses (2012)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Haase, Andrea
    Rott, Stephanie
    Mantion, Alexandre
    Graf, Philipp
    Plendl, Johanna
    Thünemann, Andreas F
    Meier, Wolfgang P
    Taubert, Andreas
    Luch, Andreas
    Reiser, Georg
    Quelle
    Toxicological sciences : an official journal of the Society of Toxicology; 126(2) — S. 457–468
    ISSN: 1096-0929
    Sprache
    Englisch
    Verweise
    DOI: 10.1093/toxsci/kfs003
    Pubmed: 22240980
    Kontakt
    Institut für Veterinär-Anatomie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53555
    anatomie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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.