Type II pyrethroid deltamethrin produces antidepressant-like effects in mice
Type II pyrethroid deltamethrin produces antidepressant-like effects in mice
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DOI：
10.1016/j.bbr.2013.09.044
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发表时间：
2013-11
影响因子：
2.7
通讯作者：
I. Takasaki;Kyohei Oose;Y. Otaki;Daisuke Ihara;M. Fukuchi;A. Tabuchi;H. Tsuneki;Y. Tabuchi;T. Kondo;A. Saitoh;M. Yamada;M. Tsuda
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作者：
I. Takasaki;Kyohei Oose;Y. Otaki;Daisuke Ihara;M. Fukuchi;A. Tabuchi;H. Tsuneki;Y. Tabuchi;T. Kondo;A. Saitoh;M. Yamada;M. Tsuda
拟除虫菊酯是一种广泛使用的杀虫剂，对哺乳动物具有低急性毒性，会影响神经元中的钠通道。在大鼠皮质神经元原代培养中，II型拟除虫菊酯溴氰菊酯（DM）显着增强脑源性神经营养因子（BDNF）mRNA的表达，发挥神经营养作用。在这项研究中，我们研究了 DM 对小鼠的抗抑郁样作用。使用强迫游泳试验 (FST) 评估 DM 的影响，并与 I 型拟除虫菊酯氯菊酯 (PM) 的影响进行比较。腹膜内注射 DM（5 和 10 mg/kg）可增加海马 BDNF mRNA 的表达，而 PM（10 mg/kg）则不增加。 DM（而非 PM）显着减少了 FST 中的不动时间，并且不影响运动活动和运动协调，表明 DM 具有抗抑郁样作用。脑室内注射 K252a 可以抑制 DM 的这种作用，K252a 是 BDNF 受体 TrkB 的抑制剂，表明 DM 的抗抑郁样作用是由 BDNF/TrkB 信号通路介导的。重复施用 DM（而非 PM）也能产生类似抗抑郁药的效果，且效果持久。本研究的结果表明，DM 具有类似抗抑郁药的特性，并且可能是开发治疗神经退行性疾病和精神疾病（包括抑郁症）的药物的可能来源。
Pyrethroids, which are widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In primary culture of rat cortical neurons, the type II pyrethroid deltamethrin (DM) markedly enhances the expression of the mRNA of brain-derived neurotrophic factor (BDNF) and exerts neurotrophic effects. In this study, we investigated the antidepressant-like effect of DM in mice. The effects of DM were assessed using the forced swimming test (FST) and were compared with those of type I pyrethroid permethrin (PM). Intraperitoneal administration of DM (5 and 10 mg/kg), but not of PM (10 mg/kg), increased the expression of BDNF mRNA in the hippocampus. DM, but not PM, significantly decreased the immobility time in the FST, and did not affect locomotor activity and motor coordination, suggesting that DM has an antidepressant-like effect. This effect of DM was inhibited by intracerebroventricular injection of K252a, which is an inhibitor of the BDNF receptor TrkB, indicating that the antidepressant-like effects of DM are mediated by BDNF/TrkB signaling pathways. Repeated administration of DM, but not of PM, also exerted antidepressant-like effects, which were long lasting. The results of the present study suggest that DM possesses antidepressant-like properties, and may be a possible source for the development of drugs to treat neurodegenerative and psychiatric disorders including depression.