| Objective In this study,female ICR mice were used to observe the effects of different concentrations of neodymium oxide nanoparticles on learning and memory in vivo by nasal instillation 45 days and to explore the possible mechanism.The purpose of this study was to explore the effects of neodymium oxide nanoparticles on the nervous system of mice.Method Two hundred healthy female ICR mice were randomly divided into control group,sham group,low dose group(L-nm,50 mg/kg·d),medium dose group(M-nm,100 mg/kg·d)and high dose group(H-nm,150 mg/kg·d)(n=40 per group).The sham group was treated with normal saline of the same volume.The control group was fed normally for 45 days without any intervention.The spatial learning and memory abilities of mice were tested by water maze test and platform jumping test.Neodymium content was measured in olfactory bulb,hippocampus and cortex of mice by inductively coupled plasma mass spectrometry(ICP-MS).The morphological changes of mice hippocampus and cortex were observed by HE staining,and the expression of glial fibrillary acidic protein(GFAP)in mice cortex was detected by immunohistochemical staining.Malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in hippocampus and cortex of mice were detected by enzyme labeling instrument.ROS was measured in hippocampus and cortex of mice by flow cytometry.Glu,Gly,GABA and DA were detected in hippocampus and cortex of mice by high performance liquid chromatography.The expression of GFAP in cortex of mice was detected by Western blot.Results(1)In the positioning navigation experiment of the third and fourth and fifth days of training,the escape latency was prolonged in 45 days of nasal drip with different concentration of nano-neodymium oxide in mice(P<0.05).In the space exploration experiment,compared with the sham group,The times of crossing the platform in 100mg/kg and 150 mg/kg nano-neodymium oxide group was decreased(P<0.05).Compared with that with the sham group and the control group,the platform quadrant distance of exposure group was decreased(P<0.05).(2)In platform jumping test,the number of errors was significantly increased in the third and fourth day of trainingcompared with that in the sham group and the control group.(P<0.05).(3)Compared with that in the sham group and the control group,in 50 mg/kg,100 mg/kg and 150 mg/kg nano-neodymium oxide group,the content of neodymium was increased in olfactory bulb(P<0.05).Compared with that in the sham group and the control group,in 150 mg/kg nano-neodymium oxide group,the content of neodymium was increased in mice cortex(P<0.05).Compared with that in the sham group and the control group,in 100 and150 mg/kg nano-neodymium oxide group,the content of neodymium was increased in mice hippocampus(P<0.05).(4)The pathological results of mice brain tissue: There was no obvious pathological changes in mice hippocampus by HE staining.The immunohistochemical staining of GFAP demonstrated that the positive expression of cells was increased in 150 mg/kg nano-neodymium oxide group.(5)Results of oxidative stress index: In the cortex,compared with the sham group and the control group,the levels of MDA of exposure group was increased.Compared with that in the sham group,the levels of SOD of exposure group was decreased.Compared with sham group and the control group,the average fluorescence intensity of ROS in total cells of cerebral cortex of mice in exposure group was increased(P<0.05).In mice hippocampus,compared with the sham group and the control group,the level of MDA in 100 mg/kg and 150 mg/kg nano-neodymium oxide group were increased.Compared with the sham group,the levels of SOD in 100 mg/kg and 150 mg/kg nano-neodymium oxide group were decreased.Compared with sham group and the control group,the average fluorescence intensity of ROS in total cells of exposed group were increased(P<0.05).In mice cortex,compared with the sham group,the content of glutamate in 150 mg/kg nano-neodymium oxide group was higher.Compared with the control group,the content of glycine and gamma-aminobutyric acid in100 mg/kg and 150 mg/kg nano-neodymium oxide group were higher.Compared with the control group,the content of gamma-aminobutyric acid in 150mg/kg nano-neodymium oxide group was higher(P<0.05).In mice hippocampus,compared with the sham group,the content of glutamic acid and glycine in 150 mg/kg nano-neodymium oxide group was higher.Compared with the sham group and control group,the content of gamma-aminobutyric acid in 150mg/kg nano-neodymium oxide group was higher,and the content of dopamine in 150 mg/kg nano-neodymium oxide group was lower than in the sham group and control group(P<0.05).The expression of GFAP in cerebral cortex in 100 mg/kg and 150mg/kg nano-neodymium oxide group of mice were increased by Western Blot compared with the sham group and control group.Compared with the sham group,expression of GFAP in cerebral cortex 50 mg/kg nano-neodymium oxide was increased(P<0.05).Conclusions: Neodymium oxide nanoparticles could reduce the learning and memory ability of mice.The mechanism might be that nano-neodymium oxide could enter the central nervous system,it related to the oxidative stress reaction,the expression of GFAP be increased and the contents of neurotransmitters in mice brain were affected. |
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