title: Deltamethrin, a type II pyrethroid insecticide, has neurotrophic effects on neurons with continuous activation of the Bdnf promoter.
abstract: Pyrethroids, widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In a primary culture of rat cortical neurons, deltamethrin (DM), a type II pyrethroid, markedly enhanced the expression of brain-derived neurotrophic factor (BDNF) exon IV-IX (Bdnf eIV-IX) mRNA. In this study, we found that DM has a neurotrophic effect on cultured neurons and investigated the mechanisms responsible for it. One μM DM increased cell survival, neurite complexity and length. Neurite complexity and length were reduced not only by a blockade of cellular excitation with GABA or Ca(2+) influx via L-type voltage-dependent calcium channels with nicardipine, but also by a blockade of TrkB, a specific receptor for BDNF, with TrkB/Fc. These data indicate DM has neurotrophic actions. DM-induced Bdnf eIV-IX mRNA expression through the calcineurin and ERK/MAPK pathways, the increase of which was reduced by GABA(A) receptor activation. Using a promoter assay, we found that Ca(2+)-responsive elements including a CRE are involved in the DM-induced activation of the Bdnf promoter IV (Bdnf-pIV). The intracellular concentration of Ca(2+) and activation of Bdnf-pIV remained elevated for, at least, 1 and 24 h, respectively. Moreover, GABA(A) receptor activation or a blockade of Ca(2+) influx even after starting the incubation with DM reduced the elevated activity of Bdnf-pIV. These data demonstrated that the prolonged activation of Bdnf-pIV occurred because of this continuous increase in the intracellular Ca(2+) concentration. Thus, DM has neurotrophic effects on neurons, likely due to prolonged activation of Bdnf promoter in neurons. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ihara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Fukuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Honma
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Tabuchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin