1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. 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 The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels. Publisher An entity responsible for making the resource available Toxicological sciences : an official journal of the Society of Toxicology Date A point or period of time associated with an event in the lifecycle of the resource 2017 2017-01 Subject The topic of the resource *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 An entity primarily responsible for making the resource Hossain Muhammad M; Liu Jason; Richardson Jason R Description An account of the resource 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 An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1093/toxsci/kfw187" target="_blank" rel="noreferrer noopener">10.1093/toxsci/kfw187</a> Rights Information about rights held in and over the resource 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