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.
Keywords: 3-MA; 3-methyladenine; Autophagy; DG; DMEM; Dulbecco's modified Eagle's medium; FBS; HFS; I/O; IPI; LC3; LC3-I/II; LTP; PE; PPF; QD; QDs; ROS; Synapse density; Synapsin-I; Synaptic plasticity; TEM; dentate gyrus; fetal bovine serum; high frequency stimulation; input/output; inter-pulse interval; light chain protein 3; long-term potentiation; mTOR; mammalian target of rapamycin; paired-pulse facilitation; phosphatidylethanolamine; quantum dot; reactive oxygen species; transmission electron microscopy.
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