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杀虫剂乙氰菊酯在体外可调节哺乳动物中枢神经系统中的神经元兴奋性。

The insecticide esfenvalerate modulates neuronal excitability in mammalian central nervous system in vitro.

作者信息

Varró Petra, Kovács Melinda, Világi Ildikó

机构信息

Department of Physiology and Neurobiology, Eötvös Loránd University, Pázmány Péter sétány 1/C, 1117 Budapest, Hungary.

MTA-KE Mycotoxins in the Food Chain Research Group, Guba Sándor utca 40, 7400 Kaposvár, Hungary.

出版信息

Toxicol Lett. 2017 Feb 5;267:39-44. doi: 10.1016/j.toxlet.2016.12.012. Epub 2016 Dec 19.

DOI:10.1016/j.toxlet.2016.12.012
PMID:28007640
Abstract

Pyrethroids are neurotoxic insecticides showing significant selective toxicity on insects over mammals, but effects on mammalian nervous system are not negligible. These substances act on the voltage-gated sodium channel, prolonging the duration of the open state. The present study focused on the effect of the pyrethroid esfenvalerate on the excitability of neuronal networks in vitro. From isolated rat brain slices, neocortical and hippocampal evoked field potentials were recorded; four concentrations (5-40μM) of esfenvalerate were tested using in vitro administration of the commercial product Sumi-Alpha 5 EC. Basic excitability and short- and long-term synaptic plasticity were studied. Application of the lowest concentration elicited epileptiform discharges in neocortex, while the highest concentration exerted a strong inhibitory effect on the excitability of both brain areas. The amplitude of population spikes in hippocampal slices was decreased by all applied concentrations. Significant decrease in basic excitability was accompanied by increase of paired-pulse facilitation in hippocampus and decreased efficacy of the development of long-term potentiation in both regions. Pyrethroids have been scarcely studied on brain slices so far, but our results are in concordance with literary data obtained on other in vitro neuronal test systems. It has been described previously that lower concentrations of pyrethroids lead to overexcitation of neurons and repetitive firing (which is in the background of hyperexcitatory symptoms occurring in case of in vivo exposure). Higher concentrations, however, may lead to depolarization block and to inhibition of neuronal firing.

摘要

拟除虫菊酯是一类神经毒性杀虫剂,对昆虫表现出显著的选择性毒性,而对哺乳动物的毒性也不可忽视。这些物质作用于电压门控钠通道,延长通道开放状态的持续时间。本研究聚焦于拟除虫菊酯乙氰菊酯对体外神经元网络兴奋性的影响。从分离的大鼠脑片中记录新皮质和海马诱发场电位;使用市售产品速灭杀丁5乳油进行体外给药,测试了四种浓度(5 - 40μM)的乙氰菊酯。研究了基本兴奋性以及短期和长期突触可塑性。最低浓度的乙氰菊酯应用引发了新皮质的癫痫样放电,而最高浓度对两个脑区的兴奋性均产生了强烈抑制作用。所有应用浓度均使海马切片中群体峰电位的幅度降低。基本兴奋性的显著降低伴随着海马中双脉冲易化的增加以及两个区域长期增强发展的效能降低。到目前为止,在脑片上对拟除虫菊酯的研究很少,但我们的结果与在其他体外神经元测试系统上获得的文献数据一致。先前已有描述,较低浓度的拟除虫菊酯会导致神经元过度兴奋和重复放电(这正是体内暴露时出现的过度兴奋症状的原因)。然而,较高浓度可能导致去极化阻滞并抑制神经元放电。

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