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Bisphenol-A exposure induced neurotoxicity and associated with synapse and cytoskeleton in Neuro-2a cells.
Toxicology in Vitro ( IF 2.6 ) Pub Date : 2020-06-05 , DOI: 10.1016/j.tiv.2020.104911
Zhihong Yin 1 , Liushuai Hua 1 , Lingli Chen 1 , Dongfang Hu 1 , Jinglong Li 1 , Zhixing An 1 , Tian Tian 1 , Hongmei Ning 1 , Yaming Ge 1
Affiliation  

Bisphenol A (BPA) is an environmental chemical that induces neurotoxic effects for human. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic morphology. The stability of the cytoskeleton in nerve cells in the brain is regulated by Tau and MAP2. This study aimed to determine the toxicity of BPA to Neuro-2a cells by investigating the synaptic and cytoskeletal damage induced in these cells by 24 h of exposure to 0 (MEM), 50, 100, 150, or 200 μM BPA or DMSO. MTT and LDH assays showed that the death rates of Neuro-2a cells increased, as the BPA concentration increased. Ultrastructural assays revealed that cells underwent nucleolar swelling as well as nuclear membrane and partial mitochondrial dissolution or condensation, following BPA exposure. Morphological analysis further revealed that compared with the cells in the control group, the cells in the BPA-treated groups shrank, became rounded, and exhibited a reduced number of synapses. BPA also significantly decreased the relative protein and mRNA expression levels of Dbn, MAP2 and Tau (P < .01), but increased the relative protein and mRNA expression levels of SYP (P < .01). These results indicated that BPA suppressed the development and proliferation of Neuro-2a cells by disrupting cellular and synaptic integrity and inflicting cytoskeleton injury.



中文翻译:

双酚A暴露引起神经毒性,并与Neuro-2a细胞中的突触和细胞骨架有关。

双酚A(BPA)是一种环境化学物质,可对人体产生神经毒性作用。突触素(SYP)和drebrin(Dbn)蛋白参与调节突触形态。Tau和MAP2调节大脑神经细胞中细胞骨架的稳定性。这项研究旨在通过调查暴露于0(MEM),50、100、150或200μMBPA或DMSO的24小时后在这些细胞中诱导的突触和细胞骨架损伤,从而确定BPA对Neuro-2a细胞的毒性。MTT和LDH分析表明,随着BPA浓度的增加,Neuro-2a细胞的死亡率增加。超微结构测定显示,在BPA暴露后,细胞经历了核仁膨胀以及核膜和部分线粒体溶解或浓缩。形态学分析进一步表明,与对照组中的细胞相比,BPA处理组中的细胞收缩,变圆并显示出减少的突触数量。BPA还显着降低了Dbn,MAP2和Tau的相对蛋白质和mRNA表达水平(P  <.01),但增加了SYP的相对蛋白和mRNA表达水平(P  <.01)。这些结果表明,BPA通过破坏细胞和突触的完整性并造成细胞骨架损伤来抑制Neuro-2a细胞的发育和增殖。

更新日期:2020-06-23
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