The Influence Of Folic Acid Supplementation On Learning And Memory Ability Of Maternal Mice Exposed To Arsenic During Pregnancy And Lactation

Objective To study the effects of arsenic exposure and folic acid supplementation during pregnancy and lactation on learning and memory ability of maternal mice,and explore its related mechanism.Methods The C57BL/6 female mice were fell into the control group,the arsenic exposed group（As group）,the folic acid supplemented group（FA group）,the arsenic exposed and folic acid supplemented group（As+FA group）,randomly.After breeding with male mice and finding the vaginal suppository,the As group and the As+FA group were exposed to arsenic via drinking water（16 mg/L）,the FA group and the As+FA group were supplemented with folic acid through diet（12 mg/kg）.The female mice were exposed to arsenic and supplemented with folic acid until the weaning of their offspring.The weights of the maternal mice during pregnancy were weighed and recorded.Seven maternal mice in the same batch（the litter interval was within 3 days）were selected from each group for Morris water maze test to detect the learning and memory ability.The arsenic contents in the urine and brain tissues of the maternal mice were measured by hydride generation atomic fluorescence.The serum folic acid contents of the maternal mice were detected by ELISA kit.The ultrastructure of hippocampus in maternal mice were observed by electron microscope,the morphology of hippocampal neurons in maternal mice were observed by Nissl staining,the dendritic complexity and the dendritic spine density of hippocampal neurons in maternal mice were observed by Golgi-cox staining,respectively.The contents of ACh,the contents of GSH,the contents of MDA,the activities of ACh E and the activities of SOD in the brain tissues of maternal mice were measured by assay kits.The expression levels of BDNF,synapsin-1,PSD-95,SOD1,SOD2,NOX4,total Nrf2,nuclear Nrf2,HO-1 and NQO1 proteins in the hippocampus of maternal mice were detected by Western blot.In addition,the expression levels of Nrf2 in the hippocampus of maternal mice were detected by immunofluorescence.Results The results of Morris water maze showed that the escape latency of maternal mice on the 6th day at the As group was higher than that at the control group（P<0.05）,and the escape latency of maternal mice on the 6th day at the As+FA group was shorter than that at the As group.The results of atomic fluorescence showed that the contents of arsenic in the brain tissues of maternal mice at the As group and As+FA group were significantly higher than that at the control group and FA group.The contents of serum folic acid of maternal mice at the control group and the As group were lower than that at the FA group and As+FA group.Nissl staining showed that there were a large number of non neuronal cells in DG area of hippocampus of maternal mice at the As group.Golgi-cox staining showed that the complexity of hippocampal DG neurons and the density of dendritic spines of maternal mice at the As group were lower than those at the control group,while maternal mice at the As+FA group was better than those at the As group.The contents of ACh,the contents of GSH and the activities of SOD in the brain tissues of maternal mice at the As group were lower than those at the control group,while the contents of ACh and the activities of SOD in the brain tissues of maternal mice at the As+FA group were higher than those at the As group.The activities of ACh E and the contents of MDA in the brain tissues of maternal mice at the As group were higher than those at the control group,while these indices at the As+FA group were lower than those at the As group.The protein expression levels of BDNF,synapsin-1,PSD-95,SOD1 and SOD2 in the hippocampus of maternal mice at the As group were lower than those indices at the control group,while the protein expression levels of BDNF,PSD-95 and SOD2 in the hippocampus of maternal mice at the As+FA group were higher than those at the As group.The protein expression levels of NOX4,NQO1,HO-1 and nuclear Nrf2 in the hippocampus of maternal mice at the As group were higher than those at the control group,while those indices at the As+FA group were lower than those at the As group.Conclusion Exposed to arsenic during pregnancy and lactation could damage the learning and memory ability of maternal mice,while supplemented with folic acid could reduce the degree of damage of maternal mice caused by arsenic exposure.The potential mechanism might be related to that arsenic could damage the morphology of neuronal cells and synapses and caused oxidant damage,while folic acid could protect neurons and synapses and repair the oxidative damage caused by arsenic.