Implications of Lead (Pb)-Induced Transcriptomic and Phenotypic Alterations in the Aged Zebrafish (Danio rerio).

IF 3.9 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES
Toxics Pub Date : 2024-10-14 DOI:10.3390/toxics12100745
Chia-Chen Wu, Danielle N Meyer, Alex Haimbaugh, Tracie R Baker
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引用次数: 0

Abstract

Lead (Pb) is a well-known neurotoxin with established adverse effects on the neurological functions of children and younger adults, including motor, learning, and memory abilities. However, its potential impact on older adults has received less attention. Using the zebrafish model, our study aims to characterize the dose-response relationship between environmentally relevant Pb exposure levels and their effects on changes in behavior and transcriptomics during the geriatric periods. We exposed two-year-old zebrafish to waterborne lead acetate (1, 10, 100, 1000, or 10,000 µg/L) or a vehicle (DMSO) for 5 days. While lower concentrations (1-100 µg/L) reflect environmentally relevant Pb levels, higher concentrations (1000-10,000 µg/L) were included to assess acute toxicity under extreme exposure scenarios. We conducted adult behavior assessment to evaluate the locomotor activity following exposure. The same individual fish were subsequently sacrificed for brain dissection after a day of recovery in the aquatic system. RNA extraction and sequencing were then performed to evaluate the Pb-induced transcriptomic changes. Higher (1000-10,000 ug/L) Pb levels induced hyperactive locomotor patterns in aged zebrafish, while lower (10-100 ug/L) Pb levels resulted in the lowest locomotor activity compared to the control group. Exposure to 100 µg/L led to the highest number of differentially expressed genes (DEGs), while 10,000 µg/L induced larger fold changes in both directions. The neurological pathways impacted by Pb exposure include functions related to neurotransmission, such as cytoskeletal regulation and synaptogenesis, and oxidative stress response, such as mitochondrial dysfunction and downregulation of heat shock protein genes. These findings emphasize a U-shape dose-response relationship with Pb concentrations in locomotor activity and transcriptomic changes in the aging brain.

铅(Pb)诱导的老龄斑马鱼(Danio rerio)转录组和表型变化的影响。
铅(Pb)是一种众所周知的神经毒素,对儿童和年轻人的神经功能(包括运动、学习和记忆能力)具有公认的不良影响。然而,铅对老年人的潜在影响却较少受到关注。利用斑马鱼模型,我们的研究旨在描述环境相关铅暴露水平之间的剂量反应关系及其对老年期行为和转录组学变化的影响。我们将两岁大的斑马鱼暴露于水性醋酸铅(1、10、100、1000 或 10,000 µg/L)或载体(DMSO)中 5 天。较低的浓度(1-100 µg/L)反映了环境中相关的铅含量,而较高的浓度(1000-10000 µg/L)则用于评估极端暴露情况下的急性毒性。我们进行了成鱼行为评估,以评估暴露后的运动活动。同样的个体鱼在水生系统中恢复一天后,我们对其进行了大脑解剖。然后进行 RNA 提取和测序,以评估铅诱导的转录组变化。与对照组相比,较高(1000-10,000 微克/升)的铅含量可诱导老龄斑马鱼出现过度活跃的运动模式,而较低(10-100 微克/升)的铅含量则导致其运动活动最低。暴露于 100 微克/升的铅可导致最多的差异表达基因(DEGs),而 10,000 微克/升的铅可诱导两个方向上更大的折叠变化。受铅暴露影响的神经通路包括与神经传递有关的功能,如细胞骨架调节和突触生成,以及氧化应激反应,如线粒体功能障碍和热休克蛋白基因下调。这些研究结果表明,老化大脑中的运动活动和转录组变化与铅浓度呈 U 型剂量反应关系。
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来源期刊
Toxics
Toxics Chemical Engineering-Chemical Health and Safety
CiteScore
4.50
自引率
10.90%
发文量
681
审稿时长
6 weeks
期刊介绍: The Journal accepts papers describing work that furthers our understanding of the exposure, effects, and risks of chemicals and materials in humans and the natural environment as well as approaches to assess and/or manage the toxicological and ecotoxicological risks of chemicals and materials. The journal covers a wide range of toxic substances, including metals, pesticides, pharmaceuticals, biocides, nanomaterials, and polymers such as micro- and mesoplastics. Toxics accepts papers covering: The occurrence, transport, and fate of chemicals and materials in different systems (e.g., food, air, water, soil); Exposure of humans and the environment to toxic chemicals and materials as well as modelling and experimental approaches for characterizing the exposure in, e.g., water, air, soil, food, and consumer products; Uptake, metabolism, and effects of chemicals and materials in a wide range of systems including in-vitro toxicological assays, aquatic and terrestrial organisms and ecosystems, model mammalian systems, and humans; Approaches to assess the risks of chemicals and materials to humans and the environment; Methodologies to eliminate or reduce the exposure of humans and the environment to toxic chemicals and materials.
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