Abstract
The mRNA expression of brain-derived neurotrophic factor (BDNF) is controlled in an activity-dependent manner through Ca2+ influx into neurons. Pyrethroids are widely used insecticides of low acute toxicity in mammals, but their effects on sodium channels are known to lead to hyperexcitation in neuronal cells of insects. In this study, we found that deltamethrin, a type II pyrethroid insecticide, was highly effective in inducing BDNF expression in culture and in the rat brain. Addition of deltamethrin to rat cortical cells in culture markedly increased the expression of BDNF exon III–V mRNA and protein, dependent upon the neuronal activity accompanying the influx of Ca2+ into neurons and the Ca2+ influx-dependent phosphorylation of extracellular signal-regulated kinases 1/2. The elevated expression was maintained for at least 48 h, even after deltamethrin was withdrawn from the culture medium. Comparison of the effects of selected pyrethroids on the expression revealed that type II but not type I pyrethroids effectively induced BDNF mRNA expression. In addition, administration of deltamethrin to rats increased the level of BDNF protein in the cerebral cortex and hippocampus. These results indicate that deltamethrin is a potent inducer of BDNF expression in neurons and that it may induce neuronal hyperexcitation if it reaches the brain.
Footnotes
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This study was supported by a grant-in-aid for Core Research for Evolutional Science and Technology from the Science and Technology Corporation of Japan and a grant-in-aid for scientific research on priority areas from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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doi:10.1124/jpet.105.092478.
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ABBREVIATIONS: BDNF, brain-derived neurotrophic factor; L-VDCC, L-type voltage-dependent calcium channel; NMDA, N-methyl-d-aspartate; BDNF-pX, brain-derived neurotrophic factor promotor I, II, III, and IV; VSSC, voltage-sensitive sodium channel; DM, deltamethrin; DMEM, Dulbecco's modified Eagle's medium; ELISA, enzyme-linked immunosorbent assay; RT-PCR, reverse transcription-polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ERK, extracellular signal-regulated kinase; TTX, tetrodotoxin; U0126, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene; U0124, 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadine.
- Received July 12, 2005.
- Accepted September 13, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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