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TOXICOLOGY

Deltamethrin, a Pyrethroid Insecticide, Is a Potent Inducer for the Activity-Dependent Gene Expression of Brain-Derived Neurotrophic Factor in Neurons

Toyama Medical and Pharmaceutical University, Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama, Japan (L.I., M.Y., K.K., D.H., A.T., M.T.); and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan (L.I., A.T., M.T.)

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 The elevated expression was maintained for at least 48 h, even after deltamethrin was withdrawn from the culture medium.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.

Address correspondence to: Dr. Masaaki Tsuda, Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan. E-mail: tsuda{at}ms.toyama-mpu.ac.jp

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