Effects Of Arsenic And Fluoride Exposure On Spatial Learning And Memory And Expression Of NMDA Receptor Subunit In The Early Days Of Rat Life

Objectives:To study the effects of sodium arsenic?NaAsO₂?and/or sodium fluoride?NaF?on spatial learning and memory,long-term potentiation?LTP?in hippocampal CA1 region,protein expression and mRNA expression levels of NMDA receptor subunits NR1,NR2A and NR2B in hippocampus in early days of rat life.To investigate the effects on learning and memory and mechanism of arsenic and/or fluoride.Methods:Sixteen healthy Sprague-Dawley rats?male and female ratio 3:1?were selected.The female rats were randomly divided into control group?tap water?,arsenic exposure group?50mg/L NaAsO₂?,fluoride exposure group?100mg/L NaF?,arsenic and fluoride combined exposure group?100mg/L NaF+50mg/L NaAsO₂?.There are three female rats in each group.Free drinking water was used to infect the virus.The start time of infection was from the day of the female and male mating to 42 days after the birth of the offspring rats?the period of the female and male mating was 20 days,and the weaning time of the rats was 21days.The offspring rats were poisoned separately after weaning?.After the end of the exposure,eight offspring rats were selected for the Morris water maze test.After the water maze experiment,two of them were selected for histopathological examination,the other six were used for LTP in hippocampal CA1 region.At the end of the LTP experiment,the rats were killed and the hippocampus was taken.Real-time fluorescence quantitative PCR?qPCR?and Western-blot were used to detect the expression of protein and mRNA of NMDA receptor subunits NR1,NR2A and NR2B.Result:The positioning search experiment showed that escape latency of the rats was statistically significant on the main effect of poisoning treatment?P<0.05?.The escape latency of arsenic and fluoride combined exposure group was more than the control group and fluoride exposure group on the third day of training,the difference was statistically significant?P<0.05?.The escape latency of arsenic and fluoride combined exposure group was more than the control group,arsenic exposure group and fluoride exposure group on the fifth day of training,the difference was statistically significant?P<0.05?.The results of space exploration experiment showed that the target quadrant residence time of fluoride exposure group and arsenic and fluoride combined exposure group was shorter than control group,the difference was statistically significant?P<0.05?.LTP amplitude of hippocampal CA1 region of the rats was statistically significant on the main effect of the toxic treatment?P<0.01?.The amplitude of LTP of arsenic exposure group,fluoride exposure group and arsenic and fluoride combined exposure group less than control group at 60 minute,the difference was statistically significant?P<0.05?.The results of qPCR showed that the levels of NR2B mRNA in arsenic poisoning group,fluoride exposure group and arsenic and fluoride combined exposure group were lower than those in the control group?P<0.05?.The effect of arsenic fluoride on the expression of NR2B mRNA interacted?P<0.05?.The results of Western-blot showed that the expression of NR2B in the arsenic and fluoride combined exposure group was significantly lower than that in the control group and the arsenic group?P<0.05?.Conclusions:1.Arsenic and fluoride alone or in combination can cause decreased learning and memory in the early days of rat life.2.Arsenic and fluoride exposure in the early days of rat life may affect the expression of NR2B by affecting the expression level of NMDA receptor subunit NR2B mRNA,which lead to changes in the structure or function of NMDA receptor,and thus affect the induction and maintenance of hippocampal LTP,eventually effect the spatial learning and memory function of the offspring rats.3.There may be interactied when arsenic and fluoride exposure combined.