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斑马鱼胚胎期汞暴露:代谢物和基因表达的改变,与视觉和行为损伤相关。

Embryonic mercury exposure in zebrafish: Alteration of metabolites and gene expression, related to visual and behavioral impairments.

机构信息

Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

出版信息

Ecotoxicol Environ Saf. 2023 May;256:114862. doi: 10.1016/j.ecoenv.2023.114862. Epub 2023 Mar 31.

Abstract

The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.

摘要

环境中存在的汞(一种重金属)以及众多工业和家庭用途中都有汞的使用,这引起了人们对其潜在健康风险的关注。然而,这种环境毒物在低浓度下的不良影响往往被低估了。有新的研究表明,汞在眼睛中的积累可能导致视力障碍,自闭症谱系障碍(ASD)特征与视力障碍之间存在共病关系。然而,人类和啮齿动物视力障碍的潜在机制具有挑战性。针对这一问题,我们以前的研究中曾使用具有视锥细胞主导的视网膜视觉系统的斑马鱼幼虫,在孵化前暴露于 100nM 氯化汞(HgCl),然后进行光暗刺激、社交测试和颜色偏好测试,以检查视觉系统与 ASD 样行为相关的功能。从原肠胚期到孵化期暴露于 HgCl 会增加黑暗中的运动活动,减少群体行为和探索行为,并损害颜色偏好。作为第一道屏障的微脊缺陷可能成为影响视力的 HgCl 毒性的主要工具。多不饱和脂肪酸(PUFAs)、亚油酸、花生四烯酸(ARA)、α-亚麻酸、二十二碳六烯酸(DHA)、硬脂酸、L-苯丙氨酸、异亮氨酸、L-赖氨酸和 N-乙酰腐胺的消耗,以及通过液相色谱-质谱(LC-MS)检测到的γ-氨基丁酸(GABA)、鞘氨醇-1-磷酸和瓜氨酸的增加,表明这些代谢物可作为影响视力和行为的视网膜损伤的生物标志物。尽管观察到 adsl、shank3a、tsc1b 和 nrxn1a 基因表达受到抑制,但在这些基因中,tsc1b 与 ASD 的相关性更为显著。总的来说,这些结果为汞毒性引起斑马鱼视觉、认知和社交缺陷的可能机制提供了新的见解。

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