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

Abstract

ABSTRACT. 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. DMinduced neurite outgrowth was abolished by U0126 and rapamycin, indicating the involvement of the mitogenactivated 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.

Influence of Nanomolar Deltamethrin on the Hallmarks of Primary Cultured Cortical Neuronal Network and the Role of Ryanodine Receptors

“…2007). It was reported that DM at 1μM increased neurite outgrowth in rat cortical neurons through endogenous BDNF/tropomyosin receptor kinase B pathways (Ihara et al. 2017).…”

“…Another factor that may also contribute to the discrepancy could be the exposure duration. We treated neurons for 48 h and 6 d commencing 3 h after plating for axon growth and dendritic complexity measurements, respectively, while in the previous study, neurons were exposed at 7 DIV for 3, 6, 12, and 24 h, respectively (Ihara et al. 2017).…”

Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity

“…Further, it is also proved that mutations that disrupt the binding of CREB can, in turn, reduce BDNF responses demonstrating the interplay between these two signaling molecules [ 21 ]. Deltamethrin, an insecticide that belongs to the pyrethroid family, increases neurite outgrowth in cortical neurons by activating the endogenous BDNF/TrkB pathway[ 39 ]. Cypermethrin, chlorpyrifos, deltamethrin, and imidacloprid exposure upregulates the mRNA and protein levels of BDNF in the brain of adult zebrafish [ 40 ].…”

Expression of SOLOIST/MRTFB i4, a novel neuronal isoform of the mouse serum response factor coactivator myocardin‐related transcription factor‐B, negatively regulates dendritic complexity in cortical neurons

“…For dendritic morphology analysis, images captured with a BX50-34LFA-1 (Olympus) fluorescent microscope were used for Sholl analysis. The previously described Sholl analysis procedure (Ihara et al, 2017;Ishikawa et al, 2010Ishikawa et al, , 2014 was performed with minor modifications. All analysis was applied to neurites of MAP2 and GFP double-positive neurons without a thin and long neurite in a blind manner.…”