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甲基汞导致鸡胚脊髓细胞线粒体超微结构变化及自噬

MeHg Causes Ultrastructural Changes in Mitochondria and Autophagy in the Spinal Cord Cells of Chicken Embryo.

作者信息

Ferreira Fabiana F, Nazari Evelise M, Müller Yara M R

机构信息

Instituto de Ciências Naturais Humanas e Sociais, UFMT, Avenida Alexandre Ferronato 1200, Setor Industrial, Sinop, MT 78557287, Brazil.

Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, UFSC, Campus Universitário, Trindade, Florianópolis, SC 88040-900, Brazil.

出版信息

J Toxicol. 2018 Aug 28;2018:8460490. doi: 10.1155/2018/8460490. eCollection 2018.

Abstract

Methylmercury (MeHg) is a known neurodevelopmental toxicant, which causes changes in various structures of the central nervous system (CNS). However, ultrastructural studies of its effects on the developing CNS are still scarce. Here, we investigated the effect of MeHg on the ultrastructure of the cells in spinal cord layers. Chicken embryos at E3 were treated with 0.1 g MeHg/50 L saline solution and analyzed at E10. Then, we used transmission electron microscopy (TEM) to identify possible damage caused by MeHg to the structures and organelles of the spinal cord cells. After MeHg treatment, we observed, in the spinal cord mantle layer, a significant number of altered mitochondria with external membrane disruptions, crest disorganization, swelling in the mitochondrial matrix, and vacuole formation between the internal and external mitochondrial membranes. We also observed dilations in the Golgi complex and endoplasmic reticulum cisterns and the appearance of myelin-like cytoplasmic inclusions. We observed no difference in the total mitochondria number between the control and MeHg-treated groups. However, the MeHg-treated embryos showed an increased number of altered mitochondria and a decreased number of mitochondrial fusion profiles. Additionally, unusual mitochondrial shapes were found in MeHg-treated embryos as well as autophagic vacuoles similar to mitophagic profiles. In addition, we observed autophagic vacuoles with amorphous, homogeneous, and electron-dense contents, similar to the autophagy. Our results showed, for the first time, the neurotoxic effect of MeHg on the ultrastructure of the developing spinal cord. Using TEM we demonstrate that changes in the endomembrane system, mitochondrial damage, disturbance in mitochondrial dynamics, and increase in mitophagy were caused by MeHg exposure.

摘要

甲基汞(MeHg)是一种已知的神经发育毒物,可导致中枢神经系统(CNS)的各种结构发生变化。然而,关于其对发育中的中枢神经系统影响的超微结构研究仍然很少。在此,我们研究了甲基汞对脊髓层细胞超微结构的影响。在E3期的鸡胚用0.1 g甲基汞/50 L盐溶液处理,并在E10期进行分析。然后,我们使用透射电子显微镜(TEM)来确定甲基汞对脊髓细胞结构和细胞器可能造成的损伤。甲基汞处理后,我们在脊髓套层中观察到大量线粒体发生改变,包括外膜破裂、嵴紊乱、线粒体基质肿胀以及线粒体内外膜之间形成液泡。我们还观察到高尔基体复合体和内质网池扩张以及出现髓磷脂样细胞质内含物。我们观察到对照组和甲基汞处理组之间的线粒体总数没有差异。然而,甲基汞处理的胚胎显示改变的线粒体数量增加,线粒体融合轮廓数量减少。此外,在甲基汞处理的胚胎中发现了异常的线粒体形状以及类似于线粒体自噬轮廓的自噬泡。此外,我们观察到含有无定形、均匀且电子致密内容物的自噬泡,类似于自噬现象。我们的结果首次表明甲基汞对发育中的脊髓超微结构具有神经毒性作用。使用透射电子显微镜我们证明,甲基汞暴露导致内膜系统变化、线粒体损伤、线粒体动力学紊乱以及线粒体自噬增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a9d/6136469/33894fcd9b88/JT2018-8460490.001.jpg

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