TY - JOUR T1 - Repression of Activity-Dependent c-<em>fos</em> and Brain-Derived Neurotrophic Factor mRNA Expression by Pyrethroid Insecticides Accompanying a Decrease in Ca<sup>2+</sup> Influx into Neurons JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1175 LP - 1182 VL - 295 IS - 3 AU - Lisa Imamura AU - Hiroshi Hasegawa AU - Kaori Kurashina AU - Ayako Hamanishi AU - Akiko Tabuchi AU - Masaaki Tsuda Y1 - 2000/12/01 UR - http://jpet.aspetjournals.org/content/295/3/1175.abstract N2 - Permethrin, a type I pyrethroid insecticide, is known to affect sodium channels of neurons and prolong sodium currents. On the other hand, the expression of brain-derived neurotrophic factor (BDNF) and c-fos genes is activated through Ca2+ influx into neurons, in an activity-dependent manner. In this study, therefore, we investigated whether permethrin influenced the Ca2+ signal-induced expression of these genes. In primary culture of mouse cerebellar granule cells (CGCs), stimulation with veratridine, a potent agonist for sodium channels, which causes membrane depolarization in neurons, induced c-fos and BDNF mRNA expression accompanying the Ca2+ influx into neurons. Pretreatment with permethrin at doses nontoxic to CGCs repressed the induction of these genes dose dependently, withtrans-permethrin more potent thancis-permethrin. Consistent with this, the increase in Ca2+ influx caused by veratridine was repressed by permethrin. The membrane depolarization induced by elevating the potassium (K+) concentration in medium (high K+) caused the activation of c-fos and BDNF genes, which was also repressed by permethrin. Immunoblotting analysis of c-Fos and a gel-mobility assay of AP-1 DNA-binding activity supported the decrease in c-Fos synthesis in permethrin-treated CGCs. The type II pyrethroid cypermethrin also affected the expression of these genes but less effectively than permethrin. Thus, pyrethroids inhibit the activity-dependent gene expression in neurons. The American Society for Pharmacology and Experimental Therapeutics ER -