CAS Key Laboratory of Brain Function and Diseases, and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China.
Biomaterials. 2013 Dec;34(38):10172-81. doi: 10.1016/j.biomaterials.2013.09.048. Epub 2013 Oct 3.
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.
众所周知，自噬是一种细胞应激反应，可以降解受损的细胞成分，许多纳米粒子都可以激活自噬。我们已经证明，广泛应用于体外诊断和细胞成像的 CdSe/ZnS 量子点（QDs）可损害齿状回（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，自噬的升高至少部分是由 QDs 在体内引起的这种突触功能障碍的原因。QDs 在 HeLa 细胞和培养的海马神经元中也引发了自噬，伴随着 GFP-轻链蛋白 3（LC3）点状斑点和自噬体形成，LC3-I 向 LC3-II 的广泛转化以及 p62 的显著减少。此外，我们发现自噬抑制剂（wortmannin、3-MA 或氯喹）抑制了 QDs 诱导的自噬流，部分阻断了 LTP 损伤，同时 QDs 在海马 CA1 区下调突触素-I 和突触缺陷。我们的研究为纳米材料引起的脑损伤提供了一种潜在的临床治疗方法，并为设计更安全的纳米粒子提供了重要依据。
