In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.
In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.
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DOI：
10.1371/journal.pone.0184475
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mortaud S
中科院分区：
文献类型：
--
作者：
Laugeray A;Herzine A;Perche O;Richard O;Montecot-Dubourg C;Menuet A;Mazaud-Guittot S;Lesné L;Jegou B;Mortaud S
越来越多的证据表明，发育过程中暴露于环境化学物质可能会改变大脑发育的过程，最终导致以后生活中的神经精神/神经退行性疾病。在本研究中，我们评估了住宅和农业应用中最常用的农药之一——合成拟除虫菊酯氯氰菊酯（CYP）对发育神经毒性（DNT）的影响。雌性小鼠从妊娠到出生后第15天，围产期暴露于低剂量的CYP（5和20 mg/kg体重）。在后代的早期生活和成年期间进行行为分析。产后分析显示，围产期暴露于CYP会干扰运动发育，但不会改变感觉和沟通技能。我们发现，在以后的生活中，暴露于cyp的后代在应对高挑战性任务和异常社交方面表现出适应不良行为。在暴露结束时对后代大脑进行的转录组学分析强调，线粒体功能障碍是cypp诱导DNT的相关病理机制。有趣的是，一些参与蛋白质平衡维持的基因也被显示出失调，这表明蛋白质的生物发生、折叠、运输和降解的改变可能显著促进了cypp相关的DNT。从监管的角度来看，本研究强调行为分析和转录组学分析是互补的工具，为更好地表征DNT提供了有用的方向，因此，应该更系统地一起使用。
Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications − the synthetic pyrethroid cypermethrin (CYP) − on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring’s early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring’s brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.
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影响因子：
--
作者：
Dubovický M;Kovačovský P;Ujházy E;Navarová J;Brucknerová I;Mach M
通讯作者：
Mach M
影响因子：
3.8
作者：
Bicks LK;Koike H;Akbarian S;Morishita H
通讯作者：
Morishita H
影响因子：
4.8
作者：
Baden, Katrina N.;Murray, James;Guillemin, Karen
通讯作者：
Guillemin, Karen
DOI：
10.1080/10253890802046281
发表时间：
2009-01
影响因子：
2.3
作者：
Grippo, Angela J.;Johnson, Alan Kim
通讯作者：
Johnson, Alan Kim
影响因子：
4.8
作者：
Ferrer I;Garcia-Esparcia P;Carmona M;Carro E;Aronica E;Kovacs GG;Grison A;Gustincich S
通讯作者：
Gustincich S