Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explo...

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Main Authors: Jasna Lojk, Lea Babič, Petra Sušjan, Vladimir Boštjan Bregar, Mojca Pavlin, Iva Hafner-Bratkovič, Peter Veranič
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/19/7030
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author Jasna Lojk
Lea Babič
Petra Sušjan
Vladimir Boštjan Bregar
Mojca Pavlin
Iva Hafner-Bratkovič
Peter Veranič
author_facet Jasna Lojk
Lea Babič
Petra Sušjan
Vladimir Boštjan Bregar
Mojca Pavlin
Iva Hafner-Bratkovič
Peter Veranič
author_sort Jasna Lojk
collection DOAJ
description Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explored the indirect effects of NPs, through consequences due to the exposure of neighboring cells to NPs. In this study, we analysed possible direct and indirect effects of NPs (polyacrylic acid (PAA) coated cobalt ferrite NP, TiO<sub>2</sub> P25 and maghemite NPs) on immortalized mouse microglial cells and differentiated CAD mouse neuronal cells in monoculture (direct toxicity) or in transwell co-culture system (indirect toxicity). We showed that although the low NP concentrations (2–25 µg/mL) did not induce changes in cell viability, cytokine secretion or NF-κB activation of microglial cells, even low NP concentrations of 10 µg/mL can affect the cells and change their secretion of protein stress mediators. These can in turn influence neuronal cells in indirect exposure model. Indirect toxicity of NPs is an important and not adequately assessed mechanism of NP toxicity, since it not only affects cells on the exposure sites, but through secretion of signaling mediators, can also affect cells that do not come in direct contact with NPs.
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spelling doaj.art-9ed2132182984edba5dae398765247002023-11-20T14:56:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119703010.3390/ijms21197030Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In VitroJasna Lojk0Lea Babič1Petra Sušjan2Vladimir Boštjan Bregar3Mojca Pavlin4Iva Hafner-Bratkovič5Peter Veranič6Group for Nano and Biotechnological Applications, Faculty of Electrical Engineering, University of Ljubljana, Trzaska cesta 25, 1000 Ljubljana, SloveniaGroup for Nano and Biotechnological Applications, Faculty of Electrical Engineering, University of Ljubljana, Trzaska cesta 25, 1000 Ljubljana, SloveniaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova ulica 19, 1000 Ljubljana, SloveniaGroup for Nano and Biotechnological Applications, Faculty of Electrical Engineering, University of Ljubljana, Trzaska cesta 25, 1000 Ljubljana, SloveniaGroup for Nano and Biotechnological Applications, Faculty of Electrical Engineering, University of Ljubljana, Trzaska cesta 25, 1000 Ljubljana, SloveniaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova ulica 19, 1000 Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaEnvironmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explored the indirect effects of NPs, through consequences due to the exposure of neighboring cells to NPs. In this study, we analysed possible direct and indirect effects of NPs (polyacrylic acid (PAA) coated cobalt ferrite NP, TiO<sub>2</sub> P25 and maghemite NPs) on immortalized mouse microglial cells and differentiated CAD mouse neuronal cells in monoculture (direct toxicity) or in transwell co-culture system (indirect toxicity). We showed that although the low NP concentrations (2–25 µg/mL) did not induce changes in cell viability, cytokine secretion or NF-κB activation of microglial cells, even low NP concentrations of 10 µg/mL can affect the cells and change their secretion of protein stress mediators. These can in turn influence neuronal cells in indirect exposure model. Indirect toxicity of NPs is an important and not adequately assessed mechanism of NP toxicity, since it not only affects cells on the exposure sites, but through secretion of signaling mediators, can also affect cells that do not come in direct contact with NPs.https://www.mdpi.com/1422-0067/21/19/7030nanoparticleneurotoxicityROScytokine secretionmicrogliaco-culture
spellingShingle Jasna Lojk
Lea Babič
Petra Sušjan
Vladimir Boštjan Bregar
Mojca Pavlin
Iva Hafner-Bratkovič
Peter Veranič
Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
International Journal of Molecular Sciences
nanoparticle
neurotoxicity
ROS
cytokine secretion
microglia
co-culture
title Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
title_full Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
title_fullStr Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
title_full_unstemmed Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
title_short Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro
title_sort analysis of the direct and indirect effects of nanoparticle exposure on microglial and neuronal cells in vitro
topic nanoparticle
neurotoxicity
ROS
cytokine secretion
microglia
co-culture
url https://www.mdpi.com/1422-0067/21/19/7030
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