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28 天经鼻吸入 PCB52(2,2',5,5'-四氯联苯)对大脑转录组的影响。

Effects of 28-day nose-only inhalation of PCB52 (2,2',5,5'-Tetrachlorobiphenyl) on the brain transcriptome.

机构信息

Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA, USA.

Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, USA.

出版信息

Toxicology. 2024 Dec;509:153965. doi: 10.1016/j.tox.2024.153965. Epub 2024 Oct 5.

DOI:10.1016/j.tox.2024.153965
PMID:39369937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11588532/
Abstract

A semi-volatile polychlorinated biphenyl (PCB) congener, PCB52, is present in the indoor air of schools; however, the effects of inhaled PCB52 on the brain have not been investigated. This study exposed male Sprague-Dawley rats at 39 days of age and female rats at 42 days of age to PCB52 for 4 hours per day over 28 consecutive days through nose-only inhalation. Neurobehavioral tests were conducted during the last 5 days of exposure. The total estimated PCB52 exposures after 28 days were 1080±20 µg/kg BW for male rats and 1140±10 µg/kg BW for female rats. PCB52 and its metabolites were detected by gas chromatography-tandem mass spectrometry in the brain, lung, and serum, with the lung showing the highest concentrations. PCB52 levels were higher in the brains of females than males. Males showed increased exploratory behavior compared to controls, whereas females exhibited decreased exploratory behavior compared to controls in the same tests. PCB52 exposure did not impact locomotor activity or working memory. Gene expression and pathway analysis in the striatum and cerebellum suggest that PCB52 inhalation causes mitochondrial dysfunction. No significant differences were observed by immunohistochemical evaluation in the density and percent area of total cells, astrocytes, or microglia in the striatum and cerebellar cortex. Our results indicate multilevel effects of inhaled PCB52 on the rat brain, from gene expression to behavioral effects.

摘要

一种半挥发性多氯联苯(PCB)同系物,PCB52,存在于学校室内空气中;然而,吸入 PCB52 对大脑的影响尚未得到研究。本研究通过鼻吸入方式,使雄性 Sprague-Dawley 大鼠在 39 日龄和雌性大鼠在 42 日龄时,每天暴露于 PCB52 4 小时,连续 28 天。在暴露的最后 5 天进行神经行为测试。28 天后,雄性大鼠的总 PCB52 暴露量估计为 1080±20μg/kg BW,雌性大鼠的总 PCB52 暴露量估计为 1140±10μg/kg BW。通过气相色谱-串联质谱法在大脑、肺和血清中检测到 PCB52 及其代谢物,其中肺部的浓度最高。雌性大鼠大脑中的 PCB52 水平高于雄性大鼠。与对照组相比,雄性大鼠表现出增强的探索行为,而雌性大鼠在相同的测试中表现出减少的探索行为。PCB52 暴露并未影响运动活动或工作记忆。纹状体和小脑中的基因表达和途径分析表明,PCB52 吸入会导致线粒体功能障碍。在纹状体和小脑皮层中,通过免疫组织化学评估,未观察到总细胞、星形胶质细胞或小胶质细胞的密度和总面积的百分比有显著差异。我们的结果表明,吸入 PCB52 对大鼠大脑产生了多层次的影响,从基因表达到行为效应。

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