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Cerium oxide nanoparticles inhibit differentiation of neural stem cells
Karolinska Inst, Div Mol Toxicol, Stockholm, Sweden.;Karolinska Inst, Inst Environm Med, Div Biochem Toxicol, Stockholm, Sweden..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
Univ Roma Tor Vergata, Dept Biol, Rome, Italy.;Univ Roma Tor Vergata, Dept Chem Sci & Technol, Rome, Italy..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9284Article in journal (Refereed) Published
Abstract [en]

Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 7, article id 9284
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Neurosciences
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URN: urn:nbn:se:uu:diva-335234DOI: 10.1038/s41598-017-09430-8ISI: 000408441600008PubMedID: 28839176OAI: oai:DiVA.org:uu-335234DiVA, id: diva2:1162812
Available from: 2017-12-05 Created: 2017-12-05 Last updated: 2018-01-13Bibliographically approved

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