从神经发育到神经退化的铅毒性单细胞研究:当前回顾与未来机遇

Maureen M. Sampson , Rachel K. Morgan , Steven A. Sloan , Kelly M. Bakulski
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引用次数: 0

摘要

人类普遍接触金属铅(Pb),并与不良的神经发育和神经退行性疾病相关。铅通过诱导氧化应激和神经炎症、改变细胞新陈代谢和置换必需金属来破坏大脑的正常功能。之前有关铅分子影响的研究都是对大块组织或靶细胞进行研究,前者会破坏所有细胞类型的信息,后者则仅限于细胞自主效应。这些方法无法代表铅暴露的全部生物学影响,因为大脑是一个由高度异质细胞组成的合作网络,在整个发育过程中,细胞的多样性和比例会随着脑区和疾病的变化而变化。有必要采用新技术来研究铅和其他环境暴露是否会改变大脑中的细胞组成,以及是否会以特定细胞类型的方式引起分子变化。现在,尖端的单细胞方法使研究能够从大块组织中解析细胞类型的特定效应。本文回顾了现有的具有全基因组分子特征的铅神经毒理学研究,并为该领域实施单细胞方法提供了前进的道路和实用的建议。
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Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects. These approaches are unable to represent the complete biological implications of Pb exposure because the brain is a cooperative network of highly heterogeneous cells, with cellular diversity and proportions shifting throughout development, by brain region, and with disease. New technologies are necessary to investigate whether Pb and other environmental exposures alter cell composition in the brain and whether they cause molecular changes in a cell-type-specific manner. Cutting-edge, single-cell approaches now enable research resolving cell-type-specific effects from bulk tissues. This article reviews existing Pb neurotoxicology studies with genome-wide molecular signatures and provides a path forward for the field to implement single-cell approaches with practical recommendations.

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来源期刊
Current opinion in toxicology
Current opinion in toxicology Toxicology, Biochemistry
CiteScore
8.50
自引率
0.00%
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0
审稿时长
64 days
期刊最新文献
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