Deltamethrin Increases Neurite Outgrowth in Cortical Neurons through Endogenous BDNF/TrkB Pathways

• Published in: Cell Structure and Function 2017, Vol.42(2), pp.141-148
• Main Authors: Ihara, Daisuke, Fukuchi, Mamoru, Katakai, Momoko, Shinoda, Yo, Katoh-Semba, Ritsuko, Furuichi, Teiichi, Ishikawa, Mitsuru, Tabuchi, Akiko, Tsuda, Masaaki
• Format: Article
• Language: English
• Subjects: Animals; Axonogenesis; BDNF; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Calcineurin; Calcineurin inhibitors; Cells, Cultured; Cerebral Cortex - cytology; Cypermethrin; Deltamethrin; Experiments; Gene expression; Insecticides - pharmacology; Laboratory animals; MAP kinase; MAPK; Morphology; mTOR; Neurite outgrowth; Neuronal Outgrowth - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Nitriles - pharmacology; Permethrin; Protein kinase; Pyrethrins - pharmacology; Pyrethroids; Rapamycin; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Tacrolimus; TOR protein; TrkB receptors; Tropomyosin
• ISSN: 0386-7196; 1347-3700
• DOI: 10.1247/csf.17015

Deltamethrin (DM), a type II pyrethroid, robustly increases brain-derived neurotrophic factor (Bdnf) expression and has a neurotrophic effect in primary cultures of rat cortical neurons. In this study, we investigated the effect of DM on neurite morphology in cultured rat cortical neurons. DM significantly increased neurite outgrowth, but this increase was abolished when the BDNF scavenger tropomyosin receptor kinase B (TrkB)-Fc was added 10 min before the DM treatment. In contrast, the addition of TrkB-Fc 1 h after the treatment did not affect DM-induced neurite outgrowth. Our previous research has indicated that type II, but not type I, pyrethroids have the ability to induce Bdnf mRNA expression, but neither permethrin nor cypermethrin, which are type I and type II pyrethroids, respectively, affected neurite outgrowth in the current study. These results suggest that this effect is not due to increased Bdnf expression, and the effect is unique to DM. We previously demonstrated that calcineurin plays a role in the DM-mediated induction of Bdnf expression. However, the calcineurin inhibitor FK506 did not significantly affect DM-induced neurite outgrowth. DM-induced neurite outgrowth was abolished by U0126 and rapamycin, indicating the involvement of the mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) pathways. Taken together, these findings suggest that DM activates endogenous BDNF/TrkB-mediated MAPK and mTOR pathways, thereby increasing neurite outgrowth.Key words: BDNF, Deltamethrin, MAPK, mTOR, Neurite outgrowth