The Research Of Aluminum Caused Genes Methylation Related To Aβ Depositing By Folic Acid Treatment In Hippocampus In Rats

Objective:To study the effects of folic acid treatment to aluminum exposure on Aβ depositing about APP/PS1/BACE1 methylation in hippocampus in rats.Methods:Forty healthy SD male rats were randomly assigned by weight into five groups: control group(n=8) and 1.08mg/kg maltolate aluminum exposure group(n=8) for treatment group,1.08mg/kg maltolate aluminum and low,medium and high dose folic acid treatment group(0.7,1.5and3.4mg/kg)(n=8),respectively,maltolate aluminum was subjected to peritoneal injection and folic acid was subjected to intragastric administration in 1ml/100 g for 60 days.1. The learning and memory ability were examined by using Morris water maze test and aluminum content in brain was determined via GFAAS(graphite furnace atomic absorption spectrometry).2. Genome-wide methylation and the expression level of A beta in hippocampus was determined via ELISA assay.3. APP, PS1, BACE1 gene methylation status was determined by MSP. The expression of m RNA and protein was determined via RT-PCR and ELISA assay.Results:1. It was revealed by Morris water maze test that target quadrant residence time and through the original position was markedly shortened as a result of aluminum exposure when compared with control group(both P<0.05).The target quadrant residence time and through the original position was extended as a result of folic acid treatment when compared with 1.08mg/kg maltolate aluminum exposure group.Both of them had statistical difference between 1.08mg/kg maltolate aluminum and(1.5,3.4mg/kg) folic acid treatment group and 1.08mg/kg maltolate aluminum exposure group(both P<0.05).It was revealed by determination of aluminium test that aluminum content in brain was markedly shortened as a result of aluminum exposure when compared with control group(both P<0.05).Both of them had statistical difference between 1.08mg/kg maltolate aluminum and(1.5,3.4mg/kg)folic acid treatment group and 1.08mg/kg maltolate aluminum exposure group(both P<0.05).It proved that learning and memory ability was markedly improved as a result of aluminum exposure. Folic acid played an important role in this trail about improving the learning and memory ability but had no influence in improving the effect of aluminium.2. It was revealed by ELISA test that considerable decrease in genome-wide methylation rate was associated with 1.08 mg/kg maltolate aluminum when compared with control group(both P<0.05). The genome-wide methylation rate was gradually increase as a result of high-dose folic acid treatment when compared with high-dose maltolate aluminum exposure group(both P<0.05).Both of them had no statistical difference when compared with control group(both P>0.05). It was revealed by ELISA test that considerable increase in A beta test was associated with 1.08 mg/kg maltolate aluminum as compared with control group(both P<0.05). The expression of A beta was gradually decrease as a result of high-dose folic acid treatment when compared with high-dose maltolate aluminum exposure group(both P<0.05).Both of them had no statistical difference when compared with control group(both P>0.05).The chronic maltolate aluminum made genome-wide methylation rate increasing, while genome-wide methylation lead to A beta protein expression increased in rat hippocampal tissue at the same time folic acid treatment was involved in the methylation process in the process of genetic modification.3. It indicated by MSP test that maltolate aluminum could change the APP gene promoter of unmethylation status in rat hippocampal tissue.Folic acid treatment could change the APP gene promoter of unmethylation status.The BACE1 gene promoter of unmethylation status changed into methylation status as a result of developing aluminum exposure. Folic acid treatment change the BACE1 gene promoter of unmethylation status caused by maltolate aluminum.Maltolate aluminum could not change the PS1 gene promoter of unmethylation status in rat hippocampal tissue. Folic acid treatment could not change the PS1 gene promoter of unmethylation status caused by maltolate aluminum.It was revealed by ELISA test and RT-PCR that aluminum exposure could increase the expression of m RNA and protein and that folic acid changed the expression of m RNA and protein caused by maltolate aluminum.Conclusions:1. Aluminum may induce learning and memory ability. Folic acid could improve its effects and there were some connections with decreasing the aluminum content in brain.2. Folic acid treatment may change the decreased learning and memory ability and decreased genome-wide methylation rate caused by aluminum.Increasing the expression of A beta in rats.They indicated folic acid supplementation may improve its effect by changing its genome-wide methylation rate.3. Aluminum may induce the APP/BACE1 gene promoter of unmethylation status and increase the expression of m RNA and protein about APP, PS1, BACE1 at the same time. Folic acid treatment may improve the effect of aluminum.4. Folic acid treatment may improve the decreased genome-wide methylation rate and the APP/BACE1 gene promoter of unmethylation status by aluminum.Decreasing the starch metabolic pathway which change the central dogma may cause Aβ depositing as a result of improving MCI.