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铅诱导的神经发育损伤和表观遗传景观:在神经障碍中的意义。

Lead-induced neurodevelopmental lesion and epigenetic landscape: Implication in neurological disorders.

机构信息

Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.

出版信息

J Appl Toxicol. 2023 Sep;43(9):1256-1271. doi: 10.1002/jat.4419. Epub 2022 Dec 13.

Abstract

Lead (Pb) was implicated in multiple genotoxic, neuroepigenotoxic, and chromosomal-toxic mechanisms and interacted with varying synaptic plasticity pathways, likely underpinning previous reports of links between Pb and cognitive impairment. Epigenetic changes have emerged as a promising biomarker for neurological disorders, including cognitive disorders, Alzheimer's disease (AD), and Parkinson's disease (PD). In the present review, special attention is paid to neural epigenetic features and mechanisms that can alter gene expression patterns upon environmental Pb exposure in rodents, primates, and zebrafish. Epigenetic modifications have also been discussed in population studies and cell experiment. Further, we explore growing evidence of potential linkage between Pb-induced disruption of regulatory pathway and neurodevelopmental and neurological disorders both in vivo and in vitro. These findings uncover how epigenome in neurons facilitates the development and function of the brain in response to Pb insult.

摘要

铅(Pb)被认为与多种遗传毒性、神经表观遗传毒性和染色体毒性机制有关,并与不同的突触可塑性途径相互作用,这可能是之前铅与认知障碍之间存在关联的报告的基础。表观遗传变化已成为神经紊乱的一种很有前途的生物标志物,包括认知障碍、阿尔茨海默病(AD)和帕金森病(PD)。在本综述中,特别关注了在啮齿动物、灵长类动物和斑马鱼中,环境铅暴露会改变基因表达模式的神经表观遗传特征和机制。在人群研究和细胞实验中也讨论了表观遗传修饰。此外,我们还探讨了越来越多的证据,表明 Pb 诱导的调节途径中断与体内和体外的神经发育和神经紊乱之间存在潜在联系。这些发现揭示了神经元中的表观基因组如何促进大脑的发育和功能,以应对 Pb 损伤。

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