Effects Of Nano-TiO₂ And Qdots On Hippocampal Synaptic Plasticity And Spatial Memory

With the development of nanotechnology and the increasing application of nanomaterials, more and more scientists begin to raise their concern on the effects of nanomaterials on human heath. Nanomaterials, because of their specific physiochemical characteristics, such as small size, could easily cross through some biological barriers and further cause potential negative effects on organisms. In this paper, we mainly used the rats as the model and separately explored the effects and the underlying mechanisms of titanium dioxide nanoparticles (TiO₂ NPs) and quantum dots (QDs) on rats'hippocampal synaptic plasticity and the changes of spatial learning and memory ability using in vivo electrophysiology, animals'behavioral tests and other biochemical techniques.Results:(1) Effects of Developmental Exposure to TiO₂ NPs on Synaptic Plasticity of HippocampusIn this study, we selected animals'development period, such as pregnancy and lactation to expose the TiO₂ NPs and explored their effects on offspring's hippocampal synaptic plasticity. Experimental groups'animals were treated with TiO₂ NPs (100mg/kg BW) orally everyday in pregnancy and lactation for 20 days separately. After the offspring matured, the following tests were carried on. ICP-MS results showed that the titanium contents in experimental groups'hippocampus were significantly increased compared to that of control group, especially in the lactation exposure group. This indicated that TiO₂ NPs indeed could cross through the blood brain barrier (BBB) and deposited in the hippocampus. In vivo field potential recordings results suggested that lactation exposure to TiO₂ NPs suppressed the I/O functions, PPR and LTP, which indicated that TiO₂ NPs exposure could decrease the efficiency of synaptic transmission and impair the short-and long-term potentiation. However, in the pregnancy TiO₂ NPs exposed groups, only PPR was decreased. Our further results showed that, after the lactation TiO₂ NPs exposure, the SOD activity and GSH contents in the hippocampus both significantly decreased when compared to the control group. Meanwhile, the contents of H₂O₂ and IL-1βin the hippocampus were significantly increased, while in the pregnancy TiO₂ NPs exposed group, only IL-1βwas increased apparently. Besides, the MDA contents in both experimental groups were not changed significantly. These results indicated that developmental exposure to TiO₂ NPs could induce ROS-mediated oxidative stress and inflammation, especially in the lactation. Integrated the results above, we thought that developmental exposure to TiO₂ NPs could attenuate the synaptic plasticity and synaptic plasticity. TiO₂ NPs induced oxidative stress and inflammation were two potential mechanisms that lead to these effects. Of course, further studied should be made to elucidate the detailed mechanisms.(2) Effects of chronic QD exposure on rats'learning and memory abilityQD is a kind of promising nanomaterials and it has been widely used in biomedical areas. With the increasing applications, studies about its biological effects are deepening. However, so far, studies about the effects of long-term QD exposure on living animals'central nervous system are limited. Our previous studies indicated that chronic QD exposure could impair the synaptic plasticity of rats'hippocampus. On this basis, we further explored whether chronic QD exposure could damage the animals'brain functions, such as learning and memory ability using animals'behavioral tests.Behavioral tests results suggested that during the first five space exploration trainings, the time for that QD treated animals found the underwater target platform (escaped latency) was longer than that of control animals. After that, the difference disappeared. Furthermore, the data from the probe tests also indicated that after the space exploration trainings the times that animals swam across the target area and the distance that animals swam around the target area were not significantly different between groups. This implied that chronic QD exposure mainly disturbed the process of memory formation. Our subsequent experiments found that chronic exposure to QD induced oxidative stress accompanied by lipid peroxidation in hippocampus. Our results further enriched the research on QD toxicity.