The Mechanisms Of Multi-Walled Carbon Nanotubes-Induced Effects Of Spatial Cognition And Synaptic Plasticity In Wistar Rat

Nanotechnology is in a rapid development stage at the present, and kinds of nanometer materials, as well as carbon nanotubes(CNTs), have been used widely in many fields. Due to their unique physical and chemical properties, CNTs have shown great applications in biomedical field, especially in the diagnosis and treatment for diseases of central nervous system. At the same time, the biological safety of CNTs has also been attended. CNTs have been proved that they could cross the blood brain barrier easily, so the neurotoxicity of CNTs should be taken into account. Several studies have reported that CNTs could induce oxidative damage of nerve cells in vitro. However, there are few studies focused on the neurotoxicity of carbon nanotubes used in vivo.Autophagy, which is a highly conserved lysosomal degradation pathway in eukaryotic cells, plays an important physiological role in maintaining the cell homeostasis. Damaged organelles and cellular wastes are swept away by the processes of autophagy. Autophagy plays complex roles in cells. On the one hand, autophagy is an essential process for cellular in response to the external stress. On the other hand, the high level of autophagy could cause cytotoxicity, and even leads to cell death. Nanomaterials have been widely recognized the new inducers of autophagy, which could induce cell death by disordering the level of autophagy. We investigated effects of spatial cognitive function and hippocampal synaptic plasticity on Wistar rats after they exposure to multi-walled carbon nanotubes(MWCNTs), and we further explored the role of autophagy in the process.The methods are as follows:Male Wistar rats were divided into 3 groups randomly: Control group, MWCNTs group and MWCNTs+CQ group. After 14 days intraperitoneal(i.p.) injection, Morris water maze was tested to the spatial cognition function of rats. Then, the long term potentiation(LTP) and depotentiation(DP) and electrophysiological experiments of Schaffer to CA1 in hippocampus were recorded. Western blot assay was used to detect the hippocampal autophagy levels(the expression of LC3II/LC3 I ratio and Beclin-1) and the expression of related synaptic proteins(NR2B, SYP). HE staining was applied to observe the structure of pyramidal neurons in hippocampal CA1 regions at the same time.The main results are as follows:In Morris water maze test, it showed that the escape latency was statistically increased in MWCNTs group compared to that in Control group in navigation stage, and there was a significant decrease of the escape latencies in MWCNTs +CQ group compared to that in MWCNTs group. In space exploration stage, quadrant dwell time and numbers of crossing platform were significantly decreased in MWCNTs group compared to those in Control group. After treatment with CQ, the two indexes were elevated. The similar results were shown in reverse navigation training stage and space exploration stage.The electrophysiological experiments showed that the fEPSP slopes of LTP were reduced in MWCNTs group compared with those of Control group, and the fEPSP slopes of DP increased significantly. CQ increased the level of fEPSP slopes of LTP dramatically. Simultaneously, the level of fEPSP slopes of DP was decreased after treatment with CQ.In Western blot test, we found that MWCNTs increased the ratio of LC3 II/LC3 I and the expression of Beclin1 significantly. At the same time, the expressions of NR2 B and SYP were decreased. In MWCNTs+CQ group, the expressions of NR2 B and SYP were elevate, and the level of LC3II/LC3 I ratio and Beclin-1 were decreased observably compared to those in MWCNTs group.HE staining showed that the pyramidal neurons of hippocampal CA1 region were full, and they arranged in order in Control group. However, pyramidal cells were shriveled, they exhibited loose and disordered. Compared with the MWCNTs group, the injuries of pyramidal neurons by MWCNTs were improved in MWCNTs+CQ group.Based on the above results, we get the following conclusion:The spatial cognitive and synaptic plasticity were damaged after rats were exposure to MWCNTs. Moreover, the hippocampal autophagy level was increased by MWCNTs. Reducing the level of autophagy through CQ could remit the spatial cognitive deficits and synaptic plasticity impairment caused by MWCNTs. We proved that autophagy was a kind of damage mechanism in this experiment. And autophagy could be used as a new target for the treatment of the central nervous system damage induced by MWCNTs.