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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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.
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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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