Ihara Daisuke, Fukuchi Mamoru, Katakai Momoko, Shinoda Yo, Katoh-Semba Ritsuko, Furuichi Teiichi, Ishikawa Mitsuru, Tabuchi Akiko, Tsuda Masaaki
Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare.
Cell Struct Funct. 2017 Oct 28;42(2):141-148. doi: 10.1247/csf.17015. Epub 2017 Sep 23.
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.
溴氰菊酯（DM）是一种II型拟除虫菊酯，能显著增加脑源性神经营养因子（Bdnf）的表达，并对大鼠皮质神经元原代培养物具有神经营养作用。在本研究中，我们调查了DM对培养的大鼠皮质神经元神经突形态的影响。DM显著增加了神经突的生长，但在DM处理前10分钟加入BDNF清除剂原肌球蛋白受体激酶B（TrkB）-Fc后，这种增加被消除。相反，处理后1小时加入TrkB-Fc并不影响DM诱导的神经突生长。我们之前的研究表明，II型拟除虫菊酯而非I型拟除虫菊酯具有诱导Bdnf mRNA表达的能力，但在本研究中，I型和II型拟除虫菊酯氯菊酯和氯氰菊酯均未影响神经突生长。这些结果表明，这种作用不是由于Bdnf表达增加所致，且该作用是DM所特有的。我们之前证明钙调神经磷酸酶在DM介导的Bdnf表达诱导中起作用。然而，钙调神经磷酸酶抑制剂FK506对DM诱导的神经突生长没有显著影响。U0126和雷帕霉素消除了DM诱导的神经突生长，表明有丝分裂原活化蛋白激酶（MAPK）和雷帕霉素靶蛋白（mTOR）信号通路参与其中。综上所述，这些发现表明DM激活内源性BDNF/TrkB介导的MAPK和mTOR信号通路，从而增加神经突生长。关键词：BDNF；溴氰菊酯；MAPK；mTOR；神经突生长
