Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system.
Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system.
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DOI：
10.1289/ehp.1003035
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发表时间：
2011-07
影响因子：
10.4
通讯作者：
Westerink RH
中科院分区：
文献类型：
--
作者：
Dingemans MM;van den Berg M;Westerink RH
背景/目的：多溴联苯醚（PBDEs）及其羟基化（OH-）或甲氧基化形式已在人体中检测到。由于这引起了对发育中的大脑的不良影响的关注，我们回顾了有关这些机制的科学文献。数据合成：许多啮齿动物研究报告了在发育期、新生儿期或成年期接触多溴二苯醚后的行为变化，其他研究记录了接触多溴二苯醚的动物大脑的细微结构和功能变化。已观察到对突触可塑性和谷氨酸-一氧化氮-环磷酸鸟苷通路的功能影响。在大脑中，已经观察到参与突触和轴突形成、神经元形态、细胞迁移、突触可塑性、离子通道和囊泡神经递质释放的基因和蛋白质的表达发生变化。细胞和分子机制包括对神经元活力（通过凋亡和氧化应激）、神经元分化和迁移、神经递质释放/摄取、神经递质受体和离子通道、钙（Ca 2+）稳态和细胞内信号传导途径的影响。
讨论：在若干内分泌终点，观察到多溴二苯醚通过羟基化作用而发生生物活化。在与神经发育相关的机制中也观察到了这一点，包括与甲状腺激素受体和转运蛋白的结合、Ca 2+稳态的破坏以及GABA和烟碱乙酰胆碱受体功能的调节。结论：羟基化（OH-）多溴二苯醚通过直接神经毒性和破坏甲状腺而对发育神经毒性的危害比其母体同系物更大，这显然需要进一步调查：（a）氧化代谢在产生多溴二苯醚活性代谢物方面的作用及其对大脑发育的影响;（B）母体和OH-多溴二苯醚在大脑中的浓度;（b）多溴二苯醚在大脑中的浓度。和c）在接触混合物期间不同环境污染物之间的相互作用，这可能会增加神经毒性。
Background/objective: Polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-) or methoxylated forms have been detected in humans. Because this raises concern about adverse effects on the developing brain, we reviewed the scientific literature on these mechanisms. Data synthesis: Many rodent studies reported behavioral changes after developmental, neonatal, or adult exposure to PBDEs, and other studies documented subtle structural and functional alterations in brains of PBDE-exposed animals. Functional effects have been observed on synaptic plasticity and the glutamate–nitric oxide–cyclic guanosine monophosphate pathway. In the brain, changes have been observed in the expression of genes and proteins involved in synapse and axon formation, neuronal morphology, cell migration, synaptic plasticity, ion channels, and vesicular neurotransmitter release. Cellular and molecular mechanisms include effects on neuronal viability
(via apoptosis and oxidative stress), neuronal differentiation and migration, neurotransmitter release/uptake, neurotransmitter receptors and ion channels, calcium (Ca2+) homeostasis, and intracellular signaling pathways. Discussion: Bioactivation of PBDEs by hydroxylation has been observed for several endocrine end points. This has also been observed for mechanisms related to neurodevelopment, including binding to thyroid hormone receptors and transport proteins, disruption of Ca2+ homeostasis, and modulation of GABA and nicotinic acetylcholine receptor function. Conclusions: The increased hazard for developmental neurotoxicity by hydroxylated (OH-)PBDEs compared with their parent congeners via direct neurotoxicity and thyroid disruption clearly warrants further investigation into a) the role of oxidative metabolism in producing active metabolites of PBDEs and their impact on brain development; b) concentrations of parent and OH-PBDEs in the brain; and c) interactions between different environmental contaminants during exposure to mixtures, which may increase neurotoxicity.
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影响因子：
10.4
作者：
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通讯作者：
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