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Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels
Muhammad M Hossain1,2, Jason Liu1, Jason R Richardson3,2
1Department of Environmental and Occupational Medicine and Environmental and Occupational Health Sciences Institute, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey.
Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 23, 2016
Summary
Pyrethroid pesticides like permethrin and deltamethrin activate microglia by interacting with voltage-gated sodium channels (VGSC). This interaction increases neuroinflammation, potentially contributing to neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Microglia are central nervous system immune cells implicated in neuroinflammation and neurodegeneration.
- Voltage-gated sodium channels (VGSC) are found on microglia and influence sodium influx and pro-inflammatory cytokine release.
- Pyrethroid pesticides target VGSC.
Purpose of the Study:
- To investigate if pyrethroid pesticides (permethrin, deltamethrin) activate microglia and increase TNF-α release via VGSC.
- To determine the role of VGSC in pyrethroid-induced microglial activation.
Main Methods:
- BV2 cells and primary microglia were treated with varying concentrations of deltamethrin or permethrin.
- Cells were co-treated with tetrodotoxin (TTX), a VGSC blocker.
- Intracellular sodium levels and TNF-α release were measured.
Main Results:
- Pyrethroids caused dose- and time-dependent increases in intracellular sodium (Na+) influx.
- Pyrethroids induced dose- and time-dependent release of tumor necrosis factor alpha (TNF-α).
- Both effects were significantly reduced by TTX, indicating VGSC involvement.
Conclusions:
- Pyrethroid pesticides can directly activate microglia by interacting with microglial VGSC.
- This activation leads to increased neuroinflammation through TNF-α release.
- Pyrethroid exposure may represent a novel mechanism contributing to neurodegeneration.
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