van Melis Lennart V J, Peerdeman Anneloes M, Huiberts Eva H W, van Kleef Regina G D M, de Groot Aart, Westerink Remco H S
Neurotoxicology Research Group, Division of Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, TD, Utrecht NL-3508, the Netherlands.
Neurotoxicology Research Group, Division of Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, TD, Utrecht NL-3508, the Netherlands..
Neurotoxicology. 2024 May;102:58-67. doi: 10.1016/j.neuro.2024.04.004. Epub 2024 Apr 9.
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.
接触氨基甲酸盐、有机磷、有机氯和拟除虫菊酯等农药与包括神经毒性在内的各种健康问题有关。尽管大多数体内研究仅使用雄性啮齿动物，但一些研究表明急性接触后存在体内性别特异性效应。由于体内研究成本高昂且需要大量动物，因此迫切需要考虑性别特异性效应的体外试验。因此，我们使用微电极阵列（MEA）记录评估了接触不同氨基甲酸盐（灭多威、涕灭威和西维因）、有机磷（毒死蜱（CPF）、毒死蜱氧磷（CPO）和3,5,6-三氯吡啶醇）、有机氯（硫丹、狄氏剂和林丹）和拟除虫菊酯（氯菊酯、α-氯氰菊酯和3-苯氧基苯甲酸（3-PBA））对性别分离的大鼠原代皮质培养物中神经网络功能的急性影响。我们的结果表明，接触氨基甲酸盐西维因以及有机磷CPF和CPO会降低神经元活性，其中CPO的作用最强。值得注意的是，CPF和CPO的（网络）爆发模式不同，CPO诱导的（网络）爆发次数较少，但强度更大。接触低微摩尔浓度的硫丹会引起过度兴奋，这很可能是由于对GABA受体的拮抗作用。有趣的是，雌性对硫丹比雄性更敏感。接触狄氏剂和林丹也会增加神经元活性，尽管程度低于硫丹且没有性别特异性效应。接触I型拟除虫菊酯氯菊酯会增加神经元活性，而接触II型拟除虫菊酯α-氯氰菊酯会强烈降低神经元活性。氯菊酯接触后观察到的增加在雄性中比在雌性中更明显。总之，这些结果表明急性接触不同类别的农药对神经元活性有不同的影响。此外，它表明MEA记录适合在体外检测性别特异性神经毒性效应。
