Objective To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides (Aβ) in cerebrospinal fluid in rats.Methods A total of 80 male Sprague-Dawley rats were randomly divided into solvent control (distilled water) group and low-,medium-,and high-dose aluminum poisoning groups (10,30,and 90 mg/kg aluminum lactate),with 20 rats in each group,and the poisoning procedure was performed by gavage for 2 months.The Morris water maze test was used to test the rats' learning and memory,Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1 (LRP-1) in rats' choroid plexus,and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.Results The Morris water maze test showed that in the place navigation test,with the increasing training time,the escape latency was significantly shortened in each group and showed significant differences between any two groups (P＜0.05).In the spatial probe test,the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43 ±5.27 s,respectively,which was significantly shorter than that in the control group and the low-dose group (15.81±3.01 s and 13.91±2.17 s)(P＜0.05).The numbers of platform crossings in the medium-and high-dose groups were 2.64± 1.39 and 1.50±0.76,respectively,which were significantly lower than those in the control group and the low-dose group (4.29±0.914 and 3.56±1.38)(P＜0.05).The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid (320.35±84.82 pg/ml and 327.68±67.51 pg/ml),which was significantlyhigher than that in the control group(203.46±74.36 pg/ml) (P＜0.05).The content of Aβ1-42 in plasma showed no significant difference between any two groups (P＞0.05),and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups (P＞0.05).The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24,P＜0.05).Conclusion Subchronic aluminum exposure may reduce learning and memory in rats,and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus,suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1,influencing the transportation of Aβ,and leading to the accumulation of Aβ.

Objective To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs) induced by aluminum.Methods The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area.The obtained single cells were cultured in DMEM with 1％ epidermal growth factor and 20％ fetal calf serum.Five days later,immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells.The well-grown cells were treated with aluminum lactate at different concentrations (0,100,400,and 1 600 μmol/L for control,low-dose,medium-dose,and high-dose groups).Forty-eight hours later,the cell viability,apoptotic rate,level of reactive oxygen species (ROS),and activity of superoxide dismutase (SOD) were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum.Results More than 95％ of the cultured cells were identified as CPECs.The medium-and high-dose groups had significantly lower cell viability than the control group (86.74％±4.03％ vs 100％,P＜0.01;81.90％±9.17％ vs 100％,P＜0.01).The high-dose group had significantly lower cell viability than the low-dose group (81.90％±9.17％ vs 92.92％±8.81％,P＜0.01).The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26％±0.99％ vs 1.29％±0.03％,P＜0.01;22.25％±1.55％ vs 1.29％±0.03％,P＜0.01) and the low-dose group (7.26％±0.99％ vs 1.68％±0.27％,P＜0.01;22.25％±1.55％ vs 1.68％±0.27％,P＜0.01).The high-dose group had a significantly higher apoptotic rate than the medium-dose group(22.25％±1.55％ vs 7.26％±0.99％,P＜0.01).The medium-and high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23％±0.41％ vs 17.24％±0.09％,P＜0.05;25.10％±1.13％ vs 17.24％±0.09％,P＜0.05) and the low-dose group (22.23％± 0.41％ vs 18.31％±0.21％,P＜0.05;25.10％±1.13％ vs 18.31％±0.21％,P＜0.05).The high-dose group had significantly higher fluorescence intensity of ROS than the medium-dose group (25.10％±1.13％ vs 22.23％± 0.41％,P＜0.05).The low-,medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(22.75±1.94) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(13.29 ±0.64) U/g Hb vs (37.35 ± 1.05) U/g Hb,P＜0.05].The medium-and high-dose groups had significantly lower SOD activity than the low-dose group [(22.75±1.94) U/g Hb vs (28.65±0.74) U/g Hb,P＜ 0.05;(13.29±0.64) U/g Hb vs (28.65±0.74) U/g Hb,P＜0.05],while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64) U/g Hb vs (22.75±1.94) U/g Hb,P＜0.05].There were no significant differences in cell viability,apoptotic rate,level of ROS,or activity of SOD between any other two groups (P＞0.05).Conclusion Aluminum lactate may induce impairment in primary cultured rat CPECs.It reduces the cell viability,elevates the apoptotic rate,and causes oxidative stress.

Objective To investigate the influence of occupational aluminum exposure on cogmtive function and its relationship with tri-methyl histone H3 lysine residues 4 points (H3K4me3) and brain-derived neurotrophic factor (BDNF) levels.Methods By cluster random sampling method,a total of 235 cases of male workers selected from a Shanxi aluminum factory were recruited in the study in September 2015.Used the occupational epidemiological investigation questionnaire,which included Mini-Mental State Examination (MMSE),Clock Drawing Test (CDT),Digit Span Test (DST,including forward test DSFT and backward test DSBT),Fuild Object Memory Evaluation (FOME) and Verbal Fluency Test (VFT),to collect workers' basic information and assess their cognitive function score.Detected the concentration of aluminum in plasma by graphite furnace atomic absorption spectrometry.Workers were divided into three groups by the 25 percentile and 75 percentile of the aluminum content,such as low,middle and high aluminum concentration groups.The concentrations of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay.Results The levels of aluminum in plasma was 134.36 (100.14,178.96) μg/L.The scores of MMSE,DSFT,DSBT,DST of high aluminum concentration group were lower than low aluminum group (27.98±1.25 vs 28.83±1.54,9.19±2.00 vs 10.64±2.87,6.08±1.63 vs 7.19±3.07,15.27±3.11 vs 17.81±4.72,all P＜0.05),the scores of CDT,FOME,VFT among three groups had no statistical significance (all P＞0.05).The expression levels of H3K4me3 and BDNF of high aluminum concentration group were lower than the low group [(18.45±9.81) ng/μg Pro vs (23.76±9.89) ng/μg Pro,(26.07±10.18) ng/ml vs (31.66±9.24) ng/ml,all P＜0.05].Multiple correlation analysis showed that aluminum concentration were negatively correlated to H3K4me3,BDNF,MMSE,DSFT,DST,respectively (rs =-0.307、-0.214、-0.252、-0.197,-0.181,all P＜0.01).Conclusion Exposure to occupational aluminum for a long time may change cognitive function,which go along with the decreasing of H3K4me3 level in lymphocyte and BDNF protein expression in plasma.

Objective To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides (Aβ) in cerebrospinal fluid in rats.Methods A total of 80 male Sprague-Dawley rats were randomly divided into solvent control (distilled water) group and low-,medium-,and high-dose aluminum poisoning groups (10,30,and 90 mg/kg aluminum lactate),with 20 rats in each group,and the poisoning procedure was performed by gavage for 2 months.The Morris water maze test was used to test the rats' learning and memory,Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1 (LRP-1) in rats' choroid plexus,and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.Results The Morris water maze test showed that in the place navigation test,with the increasing training time,the escape latency was significantly shortened in each group and showed significant differences between any two groups (P＜0.05).In the spatial probe test,the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43 ±5.27 s,respectively,which was significantly shorter than that in the control group and the low-dose group (15.81±3.01 s and 13.91±2.17 s)(P＜0.05).The numbers of platform crossings in the medium-and high-dose groups were 2.64± 1.39 and 1.50±0.76,respectively,which were significantly lower than those in the control group and the low-dose group (4.29±0.914 and 3.56±1.38)(P＜0.05).The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid (320.35±84.82 pg/ml and 327.68±67.51 pg/ml),which was significantlyhigher than that in the control group(203.46±74.36 pg/ml) (P＜0.05).The content of Aβ1-42 in plasma showed no significant difference between any two groups (P＞0.05),and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups (P＞0.05).The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24,P＜0.05).Conclusion Subchronic aluminum exposure may reduce learning and memory in rats,and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus,suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1,influencing the transportation of Aβ,and leading to the accumulation of Aβ.

Objective To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs) induced by aluminum.Methods The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area.The obtained single cells were cultured in DMEM with 1％ epidermal growth factor and 20％ fetal calf serum.Five days later,immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells.The well-grown cells were treated with aluminum lactate at different concentrations (0,100,400,and 1 600 μmol/L for control,low-dose,medium-dose,and high-dose groups).Forty-eight hours later,the cell viability,apoptotic rate,level of reactive oxygen species (ROS),and activity of superoxide dismutase (SOD) were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum.Results More than 95％ of the cultured cells were identified as CPECs.The medium-and high-dose groups had significantly lower cell viability than the control group (86.74％±4.03％ vs 100％,P＜0.01;81.90％±9.17％ vs 100％,P＜0.01).The high-dose group had significantly lower cell viability than the low-dose group (81.90％±9.17％ vs 92.92％±8.81％,P＜0.01).The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26％±0.99％ vs 1.29％±0.03％,P＜0.01;22.25％±1.55％ vs 1.29％±0.03％,P＜0.01) and the low-dose group (7.26％±0.99％ vs 1.68％±0.27％,P＜0.01;22.25％±1.55％ vs 1.68％±0.27％,P＜0.01).The high-dose group had a significantly higher apoptotic rate than the medium-dose group(22.25％±1.55％ vs 7.26％±0.99％,P＜0.01).The medium-and high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23％±0.41％ vs 17.24％±0.09％,P＜0.05;25.10％±1.13％ vs 17.24％±0.09％,P＜0.05) and the low-dose group (22.23％± 0.41％ vs 18.31％±0.21％,P＜0.05;25.10％±1.13％ vs 18.31％±0.21％,P＜0.05).The high-dose group had significantly higher fluorescence intensity of ROS than the medium-dose group (25.10％±1.13％ vs 22.23％± 0.41％,P＜0.05).The low-,medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(22.75±1.94) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(13.29 ±0.64) U/g Hb vs (37.35 ± 1.05) U/g Hb,P＜0.05].The medium-and high-dose groups had significantly lower SOD activity than the low-dose group [(22.75±1.94) U/g Hb vs (28.65±0.74) U/g Hb,P＜ 0.05;(13.29±0.64) U/g Hb vs (28.65±0.74) U/g Hb,P＜0.05],while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64) U/g Hb vs (22.75±1.94) U/g Hb,P＜0.05].There were no significant differences in cell viability,apoptotic rate,level of ROS,or activity of SOD between any other two groups (P＞0.05).Conclusion Aluminum lactate may induce impairment in primary cultured rat CPECs.It reduces the cell viability,elevates the apoptotic rate,and causes oxidative stress.

Objective To investigate the influence of occupational aluminum exposure on cogmtive function and its relationship with tri-methyl histone H3 lysine residues 4 points (H3K4me3) and brain-derived neurotrophic factor (BDNF) levels.Methods By cluster random sampling method,a total of 235 cases of male workers selected from a Shanxi aluminum factory were recruited in the study in September 2015.Used the occupational epidemiological investigation questionnaire,which included Mini-Mental State Examination (MMSE),Clock Drawing Test (CDT),Digit Span Test (DST,including forward test DSFT and backward test DSBT),Fuild Object Memory Evaluation (FOME) and Verbal Fluency Test (VFT),to collect workers' basic information and assess their cognitive function score.Detected the concentration of aluminum in plasma by graphite furnace atomic absorption spectrometry.Workers were divided into three groups by the 25 percentile and 75 percentile of the aluminum content,such as low,middle and high aluminum concentration groups.The concentrations of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay.Results The levels of aluminum in plasma was 134.36 (100.14,178.96) μg/L.The scores of MMSE,DSFT,DSBT,DST of high aluminum concentration group were lower than low aluminum group (27.98±1.25 vs 28.83±1.54,9.19±2.00 vs 10.64±2.87,6.08±1.63 vs 7.19±3.07,15.27±3.11 vs 17.81±4.72,all P＜0.05),the scores of CDT,FOME,VFT among three groups had no statistical significance (all P＞0.05).The expression levels of H3K4me3 and BDNF of high aluminum concentration group were lower than the low group [(18.45±9.81) ng/μg Pro vs (23.76±9.89) ng/μg Pro,(26.07±10.18) ng/ml vs (31.66±9.24) ng/ml,all P＜0.05].Multiple correlation analysis showed that aluminum concentration were negatively correlated to H3K4me3,BDNF,MMSE,DSFT,DST,respectively (rs =-0.307、-0.214、-0.252、-0.197,-0.181,all P＜0.01).Conclusion Exposure to occupational aluminum for a long time may change cognitive function,which go along with the decreasing of H3K4me3 level in lymphocyte and BDNF protein expression in plasma.