Mechanism Of MiRNA107 On Aluminum-induced Decreased Learning And Memory Ability And Aβ1-42 Deposition

Objective:To assess the mechanism of miRNA107 in rats’learning and memory ability decrease and the deposition of Aβ1-42.Methods:1.48 healthy male SD rats,weighing 180-220 g,randomly were divided into control group,Al（mal）₃ 10μM/kg group,Al（mal）₃ 20μM/kg group,Al（mal）₃ 40μM/kg group,each group was randomly divided into 45-day group and 60-day group.Morris water maze experiment were performed after intraperitoneal injection.Rats’cerebrum and blood were collected under anesthesia.ICP-MS was used to detect the aluminum content in rats’cerebrum and blood.ELISA was used to detect Aβ1-42 and BACE1 expression in rats’hippocampus.RT-qPCR was used to detect the expression of miRNA107 in rats’hippocampus.2.PC12 cells were cultured,the time groups were exposure to 200μmol/L Al（mal）₃for 12 hours,24 hours,36 hours,48 hours.miRNA107mimic was transferred into the cells using Entranster^TM-R4000 to establish the miRNA107 overexpression model.There were the control group,the 100μmol/L,200μmol/L,400μmol/L Al（mal）₃ groups,the negative transfection group,the miRNA107 transfection group,and the miRNA107+100μmol/L Al（mal）₃,miRNA107+200μmol/L Al（mal）₃,miRNA107+400μmol/L Al（mal）₃ groups.We collected the cell and supernatant.The expression of miRNA107 was detected by RT-qPCR,the expression of Aβ1-42 and BACE1 was detected by ELISA.Results:1.The results of animal experiments General situation of rats:The rats did not die during the experiment,the control group had normal diet and activities during the exposure.Rats in each of the exposure groups showed varying degrees of poor coat color and atrophy.Morris water maze experiment results:There was no difference in the escape latency of the rats in 45-day group（P>0.05）,the escape latency of the rats was increased in 40μM/kg group compared with that in control group in 60-day group（P<0.05）.There was no difference in the the number of the rats crossed the platform in 45-day group and 60-day group（P>0.05）.There was no difference in the time of the rats stayed on target quadrant in45-day group（P>0.05）,the time of the rats stayed on target quadrant was shorter in 20μM/kg group and 40μM/kg group compared with that in control group（P<0.05）.The aluminum content in rats’cerebrum:In 45-day group,the rats’aluminum content in 40μM/kg group was higher than it in control group（P<0.05）,in 60-day group,the rats’aluminum content in 20μM/kg and the 40μM/kg groups was higher than it in control group（P<0.05）.The aluminum content in rats’blood:The aluminum content in rats’blood was higher in 100μmol/L,200μmol/L,400μmol/L Al（mal）₃ groups than it in control group in 45-day group（P<0.05）,and it was also higher than control group in 100μmol/L,200μmol/L,400μmol/L Al（mal）₃ groups in 60-day group（P<0.05）.The results of miRNA107:The expression of miRNA107 in rats’was lower in 20μM/kg and 40μM/kg groups than it in control group in 45-day group（P<0.05）,and in 60-day group,the expression of miRNA107 in rats’in 10μM/kg,20μM/kg and the 40μM/kg groups was all lower than it in control group（P<0.05）.The results of Aβ1-42 and BACE1:The expression of Aβ1-42 and BACE1 in rats’was higher in 40μM/kg group than it in control group in 45-day group（P<0.05）,and it was higher in the 20μM/kg and 40μM/kg groups than it in control group in 60-day group（P<0.05）.2.The results of PC12 cells experiment The results of time group:The relative expression of miRNA107 in PC12 cells was lower in 24 hours,36 hours,and 48 hours groups than that in control group（P<0.05）.The expression of Aβ1-42 and BACE1 in PC12 cells was higher in 36 hours and 48 hours groups than that in control group.The results of transfection groups:The expression of miRNA107 in PC12 cells were reduced in 200μmol/L and 400μmol/L groups compared with it in control group,but they were higher in miRNA107 group and miRNA107+Al（mal）₃ groups than it in control group（P<0.05）,and there was no difference in the expression of miRNA107 in miRNA107+Al（mal）₃ groups.The Aβ1-42 and BACE1 expression were increased in 400μmol/L group,but were reduced in miRNA107 and miRNA107+Al（mal）₃ groups compared with it in control group（P<0.05）,and there was no difference in the expression of Aβ1-42 and BACE1in miRNA107+Al（mal）₃ groups.Conclusion:1.After aluminum exposure,the aluminum content in cerebrum and blood of rats were increased,the learning and memory ability of rats were declined.2.After aluminum exposure,the expression of miRNA107 was decreased,the expression of BACE1 and Aβ1-42 were increased,and the expression of miRNA107decreased earlier than other indicators.3.The increase of BACE1 expression and the deposition of Aβ1-42 induced by aluminum are caused by the decrease of early miRNA107 expression.