The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots
The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots
复制标题
自噬升高对 CdSe/ZnS 量子点引起的突触可塑性损伤的作用。
DOI：
10.1016/j.biomaterials.2013.09.048
复制
发表时间：
2013-12-01
期刊：
影响因子：
14
通讯作者：
Wang, Ming
中科院分区：
文献类型：
--
作者：
Chen, Liang;Miao, Yanyan;Wang, Ming
众所周知，自噬是一种降解受损成分的细胞应激反应，许多纳米颗粒都可以激活自噬。我们已经证实，在体外被广泛应用于诊断和细胞成像的CdSe/ZnS量子点(Qds)可以损害齿状回(DG)区的突触传递和突触可塑性，但机制尚不清楚。在这里，我们表明，自噬的升高至少是体内量子点引起的这种突触功能障碍的部分原因。量子点还可诱导HeLa细胞和培养的海马神经元自噬，并伴有GFP-轻链蛋白3(Lc3)斑点和自噬小体的形成，Lc3-I广泛转化为Lc3-II，p62显著减少。此外，我们发现自噬抑制剂(Wortmannin、3-MA或氯喹)抑制量子点诱导的自噬通量，部分阻断LTP损伤，与量子点下调突触素-I和突触缺陷在海马CA1区的作用一致。我们的研究对于为纳米材料引起的脑损伤提供潜在的临床治疗方法以及设计更安全的纳米颗粒具有重要的意义。(C)2013爱思唯尔有限公司。保留所有权利。
It is well known that autophagy, a cellular stress response to degrade damaged components, can be activated by many nanoparticles. We have demonstrated that CdSe/ZnS quantum dots (QDs), which are widely applied in vitro for diagnostics and cellular imaging, can impair synaptic transmission and synaptic plasticity in the dentate gyrus (DG) area, but the mechanism is still unclear. Here we show that elevated autophagy is at least partly responsible for this synaptic dysfunction induced by QDs in vivo. QDs elicited autophagy in the HeLa cells and cultured hippocampal neurons as well, accompanied with GFP-light chain protein 3 (LC3) puncta dots and autophagosome formation, extensive conversion of LC3-I to LC3-II and a significant decrease of p62. Furthermore, we found that autophagy inhibitors (wortmannin, 3-MA or chloroquine) suppressed QDs-induced autophagic flux, partly blocked LTP impairment, coincident with down-regulation of synapsin-I and synapse deficits by QDs in the hippocampal CA1 area. Our studies have important implications in providing a potential clinical remedy for brain damage caused by nanomaterials and in designing safer nanoparticles. (C) 2013 Elsevier Ltd. All rights reserved.