Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels.

Title

Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels.

Creator

Hossain Muhammad M; Liu Jason; Richardson Jason R

Publisher

Toxicological sciences : an official journal of the Society of Toxicology

Date

2017
2017-01

Description

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.

Subject

*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

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

112–123

Issue

1

Volume

155

Citation

Hossain Muhammad M; Liu Jason; Richardson Jason R, “Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels.,” NEOMED Bibliography Database, accessed November 28, 2021, https://neomed.omeka.net/items/show/4211.

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