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Developmental neurotoxic effects of a low dose of TCE on a 3-D neurosphere system

机译:3D神经圈系统低剂量TCE的发育神经毒性作用

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Trichloroethylene (TCE) is one of the industrial toxic byproducts that now persist in the air, soil, and water. Several studies have already illustrated the toxic effect of high doses of TCE on the biological functions of several organs. This study aims to highlight the toxic impact of a low dose of TCE (1 μmol/L) on the development of rat neural stem cells (NSCs). The subventricular zones (SVZ) of rat pup’s brains were collected and minced, and the harvested cells were cultured in the presence of neural growth factors B27/N2 to develop neurospheres. The cells were then exposed to a dose of 1 μmol/L TCE for 1 or 2 weeks. The outcomes indicated a remarkable inhibitory effect of TCE on the differentiation capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect of TCE exposure. PCR results revealed a TCE-mediated suppression of the expression of the antioxidant enzyme SOD1. This paper illustrates, for the first time, a detailed examination of the toxic effects of an environmentally low dose of TCE on NCSs at the transcriptional, translational, and functional levels.
机译:三氯乙烯(TCE)是现在在空气,土壤和水中持续存在的工业毒性副产品之一。几项研究已经说明了高剂量TCE对几个器官的生物学功能的毒性作用。本研究旨在突出低剂量TCE(1μmol/ L)对大鼠神经干细胞(NSCs)的发育的毒性影响。收集并切碎大鼠幼粒大脑的胎盘区(SVZ),并在神经生长因子B27 / N 2存在下培养收获的细胞以开发神经球。然后将细胞暴露于1μmol/ L TCE的剂量1或2周。结果表明,TCE对NSCs的分化能力的显着抑制作用,其通过半胶质细胞标志物GFAP的下调证实,TCE对NSCs的增殖的抑制作用是通过神经圈直径的减少来鉴定NSCs的抑制作用,ki67表达,和G1 / S期的细胞周期停滞。 Inmunolabling与Annexin V表示TCE暴露的凋亡效应。 PCR结果揭示了TCE介导的抗氧化酶SOD1表达的抑制。本文首次说明了对转录,平移和功能水平在NCS上的环境低剂量TCE的毒性作用的详细检查。

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