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Text
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URL Address
<a href="http://doi.org/10.1093/toxsci/kfw187" target="_blank" rel="noreferrer noopener">http://doi.org/10.1093/toxsci/kfw187</a>
Pages
112–123
Issue
1
Volume
155
Dublin Core
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Title
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Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels.
Publisher
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Toxicological sciences : an official journal of the Society of Toxicology
Date
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2017
2017-01
Subject
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*deltamethrin; *intracellular sodium.; *microglia; *neurodegeneration; *neuroinflammation; *permethrin; *pyrethroids; *tetrodotoxin; *tumor necrosis factor; *voltage-gated sodium channels; Animals; Cell Line; Dose-Response Relationship; Drug; Inbred C57BL; Insecticides/*toxicity; Ion Channel Gating/*drug effects; Mice; Microglia/*drug effects/metabolism; Pyrethrins/*toxicity; Sodium Channels/*drug effects; Transformed; Tumor Necrosis Factor-alpha/metabolism
Creator
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Hossain Muhammad M; Liu Jason; Richardson Jason R
Description
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Microglia are considered to be the resident immune cells of the central nervous system and contribute significantly to ongoing neuroinflammation in a variety of neurodegenerative diseases. Recently, we and others identified that voltage-gated sodium channels (VGSC) are present on microglia cells and contribute to excessive accumulation of intracellular Na(+ )and release of major pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Based on this finding and the fact that pyrethroid pesticides act on VGSC, we hypothesized that exposure of microglia to the pyrethroid pesticides, permethrin and deltamethrin, would activate microglia and increase the release of TNF-alpha. BV2 cells or primary microglia were treated with 0-5 microM deltamethrin or permethrin in the presence or absence of tetrodotoxin (TTX), a VGSC blocker for 24-48 h. Both pyrethroids caused a rapid Na(+ )influx and increased accumulation of intracellular sodium [(Na(+))i] in the microglia in a dose- and time-dependent manner, which was significantly reduced by TTX. Furthermore, deltamethrin and permethrin increased the release of TNF-alpha in a dose- and time-dependent manner, which was significantly reduced by pre-treatment of cells with TTX. These results demonstrate that pyrethroid pesticides may directly activate microglial cells through their interaction with microglial VGSC. Because neuroinflammation plays a key role in many neurodegenerative diseases, these data provide an additional mechanism by which exposure to pyrethroid insecticides may contribute to neurodegeneration.
Identifier
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<a href="http://doi.org/10.1093/toxsci/kfw187" target="_blank" rel="noreferrer noopener">10.1093/toxsci/kfw187</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*deltamethrin
*intracellular sodium.
*Microglia
*neurodegeneration
*Neuroinflammation
*permethrin
*pyrethroids
*tetrodotoxin
*tumor necrosis factor
*Voltage-gated sodium channels
2017
Animals
Cell Line
Department of Pharmaceutical Sciences
Dose-Response Relationship
Drug
Hossain Muhammad M
Inbred C57BL
Insecticides/*toxicity
Ion Channel Gating/*drug effects
Liu Jason
Mice
Microglia/*drug effects/metabolism
NEOMED College of Pharmacy
Pyrethrins/*toxicity
Richardson Jason R
Sodium Channels/*drug effects
Toxicological sciences : an official journal of the Society of Toxicology
Transformed
Tumor Necrosis Factor-alpha/metabolism