Effects Of Arsenic Exposure On D-serine Metabolism In The Hippocampus Of Offspring Nmice At Differernt Developmental Stages

ObjectiveThe aim of this study was to investigate the effects of arsenic exposure on the metabolism of D-serine in hippocampus of mice and to explore mechanisms of learning and memory in different developmental stages.And provide experimental reference data for further elaboration of the neurotoxicity mechanism of arsenic exposure,and provide the theoretical basis for guiding the prevention and treatment of arsenic chronic poisoning.MethodsTo set up the model of offspring mice exposed to arsenic at different developmental stages.Concentrations of arsenic were 0,15,30 and 60 mg/L in drinking water respectively.The ability of spatial learning and memory of pups was measured by Morris water maze test.Pups were sacrificed in postnatal day(PND)10,20 and 40,and the hippocampus was immediately dissected out.weight of mice were recorded to in different development stages of seed.The contents of D-serine were detected by high performance liquid chromatography(HPLC).Expressions of serine racemase(SR),D-amino acid oxidase(DAAO),alanine-serine-cysteine transporter-1(asc-1),the subunits of N-methyl-D-aspartate receptor(NMDAR)NR1,NR2A and NR2B were examined by Western blot.ResultsPND 20,The body weights of mice of in 60 mg/L arsenic exposed group were significantly lower than those in control groups and 15 mg/L arsenic exposed group;PND 40,the body weights of mice in 30 and 60 mg/L arsenic exposed groups were significantly lower than arsenic control groups;60 mg/L arsenic exposed group were significantly lower than those in 15 and 30 mg/L arsenic exposed group.Spatial learning and memory ability of mice was evaluated on PND 40 by Morris water maze.The results showed that escape latency in 60 mg/L arsenic exposed group was significantly higher than that in control group since the fourth day of training.On the other hand,in the probe trail,the time spent in the quadrant in 60 mg/L arsenic exposed group was significantly longer than in the control group.The contents of D-serine were detected by high performance liquid chromatography(HPLC),the results showed that the contents of D-serine in 60 mg/L arsenic exposed group was lower than that in the control group in PND 10,but the differences among the arsenic exposed groups were not significant in PND 20 and 40.Level of SR protein in 60 mg/L arsenic exposed group was significantly lower than that in 0 and 15 mg/L arsenic exposed groups in PND 10;Levels of SR protein in 30 and 60 mg/L arsenic exposed groups were significantly lower than those in control group in PND 20;Levels of SR protein in 30 and 60 mg/L arsenic exposed group were significantly lower than those in 0 and 15 mg/L arsenic exposed groups in PND 40;Levels of DAAO protein in 30 and 60 mg/L arsenic exposed groups were significantly higher than those in control group in PND 10 and 40;Level of DAAO protein in 60 mg/L arsenic exposed group was significantly higher than those in control group in PND 20;Level of asc-1 protein of PND 10 mice in the arsenic exposed groups were significantly higher than those in the control;but the differences among the arsenic exposed groups were not significant in PND 20 and 40.Levels of NR1 protein in 30 and 60 mg/L arsenic exposed groups were significantly lower than those in control group in PND 10,level of NR1 protein in 60 mg/L arsenic exposed group was significantly lower than 15 mg/L arsenic exposed group;Levels of NR1 protein in 30 and 60 mg/L arsenic exposed groups were significantly lower than those in 0 and 15 mg/L arsenic exposed groups in PND 20;but the differences among the arsenic exposed groups were not significant in PND 40.Levels of NR2A protein in 30 and 60 mg/L arsenic exposed groups were significantly lower than those in control group in PND 10,Levels of NR2A protein of PND 20 mice in the arsenic exposed groups were significantly lower than those in control,group the level of NR2A protein in 60 mg/L arsenic exposed group was significantly lower than that in 15 and 30 mg/L arsenic exposed groups;the level of NR2A protein in 30 and 60 mg/L arsenic exposed groups were significantly lower than that in control group in PND40;Level of NR2B protein in 30 and 60 mg/L arsenic exposed groups was significantly lower than that in 0 and 15 mg/L arsenic exposed groups in PND 10 and 40,level of NR2B protein in 60 mg/L arsenic exposed group was significantly lower than that in 30 mg/L arsenic exposed group;Level of NR2B protein in the arsenic exposed groups were significantly lower than those in the control group,Level of NR2B protein in 30 and 60 mg/L arsenic exposed groups was significantly lower than that in 15 mg/L arsenic exposed group in PND 20.Conclusions1.Arsenic exposure can reduce the ability of learning and memory of offspring mice.2.Arsenic exposure can decrease the level of D-serine in hippocampus of offspring mice.3.Arsenic exposure can decrease the level of SR and increase the levels of DAAO and asc-1 in the hippocampus of offspring mice,which may affect the metabolism of D-serine.4.Arsenic exposure can decrease the levels of NR1,NR2A and NR2B,which may affect the ability of learning and memory.