Cognitive deficits induced by multi-walled carbon nanotubes via the autophagic pathway.
Multi-walled carbon nanotubes (MWCNTs) have shown potential applications in many fields, especially in the field of biomedicine. Several studies have reported that MWCNTs induce apoptosis and oxidative damage in nerve cells during in vitro experiments. However, there are few studies focused on the neurotoxicity of MWCNTs used in vivo. Many studies have reported that autophagy, a cellular stress response to degrade damaged cell components, can be activated by diverse nanoparticles. In this study, we investigated the neurotoxic effects of MWCNTs on hippocampal synaptic plasticity and spatial cognition in rats. Then, we used an inhibitor of autophagy called chloroquine (CQ) to examine whether autophagy plays an important role in hippocampal synaptic plasticity, since this was damaged by MWCNTs. In this study, adult male Wister rats were randomly divided into three groups: a control group, a group treated with MWCNTs (2.5mg/kg/day) and a group treated with MWCNTs+CQ (20mg/kg/day). After two-weeks of intraperitoneal (i.p.) injections, rats were subjected to the Morris water maze (MWM) test, and the long-term potentiation (LTP) and other biochemical parameters were determined. Results showed that MWCNTs could induce cognitive deficits, histopathological alteration and changes of autophagy level (increased the ratio of LC3 II /LC3 I and the expression of Beclin-1). Furthermore, we found that CQ could suppress MWCNTs-induced autophagic flux and partly rescue the synapse deficits, which occurred with the down-regulation of NR2B (a subunit of NMDA receptor) and synaptophysin (SYP) in the hippocampus. Our results suggest that MWCNTs could induce cognitive deficits in vivo via the increased autophagic levels, and provide a potential strategy to avoid the adverse effects of MWCNTs.
College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.
Jing
J
Gao
College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.
Xiaochen
X
Zhang
College of Life Science, Nankai University, Tianjin 300071, China.
Mei
M
Yu
Science and Technology Research Institute, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK.
Guogang
G
Ren
College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. Electronic address: zhuoyang@nankai.edu.cn.
Zhuo
Z
Yang
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D002738:Chloroquine / Q000633:toxicity; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D037742:Nanotubes, Carbon; D002738:Chloroquine
Autophagy; Chloroquine; Cognitive deficits; MWCNTs; Rats