Cognitive And Locomotor Activity Changes Of Kunming Mice Induced By Single-walled Carbon Nanotubes

Nowadays, nanoscience is in a stage of rapid development, while has been widely applied in many fields, the safety of nanomaterials were also been great concern.Carbon nanotubes (CNT) is an important member of the family of nanomaterials, single-walled carbon nanotubes (SWCNTs) as a widely used nanomaterial, has shown great application value in the field of biological medicine, especially in the field of the nervous system. However, the in vivo studies of the neurotoxicity of SWCNTs have limited. This study through the behavior changes of Kunming mice after SWCNTs exposure, brain tissue damage and toxicity mechanism research, to evaluate the neurotoxicity of SWCNTs and the possible mechanism of injury, and use the protective agent to protect brain tissue to provide experimental support for the safe application of SWCNTs.This research through the behavior study (Morris water maze, Open field test), and brain tissue histopathological examination (H&E staining, Nissl staining) to evaluate the impact of SWCNTs exposure on mice behavior as well as the extent of the damage of brain tissue. Through the detection of oxidative stress indicators (reactive oxygen species, ROS; malondialdehyde, MDA; glutathione, GSH), inflammation indicators (nuclear factor kappa-B, NF-κB; tumor necrosis factor alpha, TNF-a; interleukin-1beta, IL-1β) and apoptosis index (cysteine-aspartic acid protease3, Caspase-3) to explore the possible mechanism of the neurotoxicity of SWCNTs.By adding ascorbic acid as a protective agent, to explore the protective effects of ascorbic acid and the mechanism.The results showed that tail vein injection of6.25and12.5mg/kg/day SWCNTs, in the Morris water maze, the learning and memory ability of mice decreased, the mice showed a cognitive deficit. In the open field test, the mice showed a decreased locomotor activity. Mouse brain tissue histopathological examination showed that the hippocampus CA1pyramidal neurons damage, and had plenty of nissl substance lost. Mouse brain tissue oxidative stress, inflammation, and apoptosis index determination results show that the ROS level in the brain tissue and MDA content appeared a significant increased and GSH levels appeared a significant decreased, transcription factors NF-κ B significantly increaseed, the expression level of inflammatory factor TNF-a and IL-1β were also significantly increased, apoptosis factors Caspase-3activity also increased significantly.3.125mg/kg/day SWCNTs exposed only induced slight negative effect on the mice, the rise of ROS have been found in the brain, but inflammation and apoptosis index did not appear significantly changed.The study shows that6.25and12.5mg/kg/day SWCNTs exposure can induced Kunming mice cognitive deficit, locomotor activity decreased and brain tissue damaged. Oxidative stress, inflammation, and apoptosis may be one of the mechanisms of brain tissue damage,3.125mg/kg/day for mice in the experiments is a relatively safe use concentration. Down-regulation of oxidative stress, inflammation and apoptosis was proposed to explain the neuroprotective effects of ascorbic acid.