急性杀虫剂暴露对体外大鼠皮层培养神经元活动的影响

IF 3.4 3区 医学 Q2 NEUROSCIENCES Neurotoxicology Pub Date : 2024-04-09 DOI:10.1016/j.neuro.2024.04.004
Lennart V.J. van Melis, Anneloes M. Peerdeman, Eva H.W. Huiberts, Regina G.D.M. van Kleef, Aart de Groot, Remco H.S. Westerink
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引用次数: 0

摘要

接触杀虫剂(如氨基甲酸酯、有机磷、有机氯和拟除虫菊酯)与各种健康问题(包括神经毒性)有关。虽然大多数体内研究只使用雄性啮齿动物,但一些研究显示,急性接触后,体内的性别特异性效应也会产生影响。由于体内研究成本高昂且需要大量动物,因此迫切需要考虑到性别特异性效应的体外检测方法。因此,我们评估了急性接触不同的氨基甲酸酯类(灭多威、涕灭威和西维因)、有机磷类(毒死蜱(CPF)、毒死蜱-氧磷(CPO)和 3,5,6-三氯吡啶醇)、有机氯类(硫丹、狄氏剂和林丹)的影响、和林丹)和拟除虫菊酯(氯菊酯、甲型氯氰菊酯和 3-苯氧基苯甲酸(3-PBA))对大鼠初级皮层神经元网络功能的影响。我们的研究结果表明,接触氨基甲酸酯类西维因以及有机磷类氯化石蜡和氯化石蜡会降低神经元的活性,其中氯化石蜡的作用最强。值得注意的是,CPF 和 CPO 的(网络)突发性模式不同,CPO 诱导的(网络)突发性更少,但更强烈。暴露于低微摩尔水平的硫丹会引起过度兴奋,这很可能是由于硫丹对 GABA 受体的拮抗作用。有趣的是,雌性比雄性对硫丹更敏感。接触狄氏剂和林丹也会增加神经元的活动,尽管其程度低于硫丹,而且没有性别特异性影响。接触 I 型拟除虫菊酯氯菊酯会增加神经元的活性,而接触 II 型拟除虫菊酯甲型氯菊酯则会大大降低神经元的活性。暴露于氯菊酯后,男性的神经元活动增加比女性更明显。这些结果表明,急性接触不同种类的杀虫剂会对神经元活动产生不同的影响。此外,它还表明 MEA 记录适合于体外检测性别特异性神经毒性效应。
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Effects of acute insecticide exposure on neuronal activity in vitro in rat cortical cultures

Exposure to pesticides, such as carbamates, organophosphates, organochlorines and pyrethroids, has been linked to various health problems, including neurotoxicity. Although most in vivo studies use only male rodents, some studies have shown in vivo sex-specific effects after acute exposure. Since in vivo studies are costly and require a large number of animals, in vitro assays that take sex-specific effects into account are urgently needed. We therefore assessed the acute effects of exposure to different carbamates (methomyl, aldicarb and carbaryl), organophosphates (chlorpyrifos (CPF), chlorpyrifos-oxon (CPO) and 3,5,6-trichloropyridinol), organochlorines (endosulfan, dieldrin and lindane) and pyrethroids (permethrin, alpha-cypermethrin and 3-phenoxy-benzoic acid (3-PBA)) on neuronal network function in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings. Our results indicate that exposure to the carbamate carbaryl and the organophosphates CPF and CPO decreased neuronal activity, with CPO being the most potent. Notably, (network) burst patterns differed between CPF and CPO, with CPO inducing fewer, but more intense (network) bursts. Exposure to low micromolar levels of endosulfan induced a hyperexcitation, most likely due to the antagonistic effects on GABA receptors. Interestingly, females were more sensitive to endosulfan than males. Exposure to dieldrin and lindane also increased neuronal activity, albeit less than endosulfan and without sex-specific effects. Exposure to type I pyrethroid permethrin increased neuronal activity, while exposure to type II pyrethroid alpha-cypermethrin strongly decreased neuronal activity. The increase seen after permethrin exposure was more pronounced in males than in females. Together, these results show that acute exposure to different classes of pesticides exerts differential effects on neuronal activity. Moreover, it shows that MEA recordings are suited to detect sex-specific neurotoxic effects in vitro.

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来源期刊
Neurotoxicology
Neurotoxicology 医学-毒理学
CiteScore
6.80
自引率
5.90%
发文量
161
审稿时长
70 days
期刊介绍: NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.
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