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Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation
BACKGROUND: Silica nanoparticles (SiO(2)-NPs) are naturally enriched and broadly utilized in the manufacturing industry. While previous studies have demonstrated toxicity in neuronal cell lines after SiO(2)-NPs exposure, the role of SiO(2)-NPs in neurodegeneration is largely unknown. Here, we evalua...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029039/ https://www.ncbi.nlm.nih.gov/pubmed/29970116 http://dx.doi.org/10.1186/s12989-018-0263-3 |
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author | You, Ran Ho, Yuen-Shan Hung, Clara Hiu-Ling Liu, Yan Huang, Chun-Xia Chan, Hei-Nga Ho, See-Lok Lui, Sheung-Yeung Li, Hung-Wing Chang, Raymond Chuen-Chung |
author_facet | You, Ran Ho, Yuen-Shan Hung, Clara Hiu-Ling Liu, Yan Huang, Chun-Xia Chan, Hei-Nga Ho, See-Lok Lui, Sheung-Yeung Li, Hung-Wing Chang, Raymond Chuen-Chung |
author_sort | You, Ran |
collection | PubMed |
description | BACKGROUND: Silica nanoparticles (SiO(2)-NPs) are naturally enriched and broadly utilized in the manufacturing industry. While previous studies have demonstrated toxicity in neuronal cell lines after SiO(2)-NPs exposure, the role of SiO(2)-NPs in neurodegeneration is largely unknown. Here, we evaluated the effects of SiO(2)-NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures. RESULTS: Male C57BL/6 N mice (3 months old) were exposed to either vehicle (sterile PBS) or fluorescein isothiocyanate (FITC)-tagged SiO(2)-NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl staining, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure. CONCLUSIONS: Intranasal instillation of SiO(2)-NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12989-018-0263-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6029039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60290392018-07-09 Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation You, Ran Ho, Yuen-Shan Hung, Clara Hiu-Ling Liu, Yan Huang, Chun-Xia Chan, Hei-Nga Ho, See-Lok Lui, Sheung-Yeung Li, Hung-Wing Chang, Raymond Chuen-Chung Part Fibre Toxicol Research BACKGROUND: Silica nanoparticles (SiO(2)-NPs) are naturally enriched and broadly utilized in the manufacturing industry. While previous studies have demonstrated toxicity in neuronal cell lines after SiO(2)-NPs exposure, the role of SiO(2)-NPs in neurodegeneration is largely unknown. Here, we evaluated the effects of SiO(2)-NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures. RESULTS: Male C57BL/6 N mice (3 months old) were exposed to either vehicle (sterile PBS) or fluorescein isothiocyanate (FITC)-tagged SiO(2)-NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl staining, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure. CONCLUSIONS: Intranasal instillation of SiO(2)-NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12989-018-0263-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-03 /pmc/articles/PMC6029039/ /pubmed/29970116 http://dx.doi.org/10.1186/s12989-018-0263-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research You, Ran Ho, Yuen-Shan Hung, Clara Hiu-Ling Liu, Yan Huang, Chun-Xia Chan, Hei-Nga Ho, See-Lok Lui, Sheung-Yeung Li, Hung-Wing Chang, Raymond Chuen-Chung Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title | Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title_full | Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title_fullStr | Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title_full_unstemmed | Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title_short | Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation |
title_sort | silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through mapk activation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029039/ https://www.ncbi.nlm.nih.gov/pubmed/29970116 http://dx.doi.org/10.1186/s12989-018-0263-3 |
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