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Influence of extracellular zinc on M1 microglial activation
Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327400/ https://www.ncbi.nlm.nih.gov/pubmed/28240322 http://dx.doi.org/10.1038/srep43778 |
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author | Higashi, Youichirou Aratake, Takaaki Shimizu, Shogo Shimizu, Takahiro Nakamura, Kumiko Tsuda, Masayuki Yawata, Toshio Ueba, Tetuya Saito, Motoaki |
author_facet | Higashi, Youichirou Aratake, Takaaki Shimizu, Shogo Shimizu, Takahiro Nakamura, Kumiko Tsuda, Masayuki Yawata, Toshio Ueba, Tetuya Saito, Motoaki |
author_sort | Higashi, Youichirou |
collection | PubMed |
description | Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30–60 μM ZnCl(2) resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia–reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory. |
format | Online Article Text |
id | pubmed-5327400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53274002017-03-03 Influence of extracellular zinc on M1 microglial activation Higashi, Youichirou Aratake, Takaaki Shimizu, Shogo Shimizu, Takahiro Nakamura, Kumiko Tsuda, Masayuki Yawata, Toshio Ueba, Tetuya Saito, Motoaki Sci Rep Article Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30–60 μM ZnCl(2) resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia–reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory. Nature Publishing Group 2017-02-27 /pmc/articles/PMC5327400/ /pubmed/28240322 http://dx.doi.org/10.1038/srep43778 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Higashi, Youichirou Aratake, Takaaki Shimizu, Shogo Shimizu, Takahiro Nakamura, Kumiko Tsuda, Masayuki Yawata, Toshio Ueba, Tetuya Saito, Motoaki Influence of extracellular zinc on M1 microglial activation |
title | Influence of extracellular zinc on M1 microglial activation |
title_full | Influence of extracellular zinc on M1 microglial activation |
title_fullStr | Influence of extracellular zinc on M1 microglial activation |
title_full_unstemmed | Influence of extracellular zinc on M1 microglial activation |
title_short | Influence of extracellular zinc on M1 microglial activation |
title_sort | influence of extracellular zinc on m1 microglial activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327400/ https://www.ncbi.nlm.nih.gov/pubmed/28240322 http://dx.doi.org/10.1038/srep43778 |
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