Objective: To investigate the effects of lithium on cognitive function and metabolism of Amyloid-beta Protein Precursor (APP) and tau phosphorylation in rats chronically exposed to aluminum. Methods: Twenty-four chron...Objective: To investigate the effects of lithium on cognitive function and metabolism of Amyloid-beta Protein Precursor (APP) and tau phosphorylation in rats chronically exposed to aluminum. Methods: Twenty-four chronically aluminum-exposed rats were randomly divided into 2 groups: a lithium-treatment group and a non-treatment group (n=12 per group). Lithium chloride was administered to the lithium-treatment group via gastric gavage daily for 6 weeks (200 mg/kg·d LiCl), while the non-treatment group was administered the same volume of sodium chloride by the same means. An additional control group (n=12) received no intervention. Memory function was evaluated by the Morris water maze test. Aβ was measured by immunohistochemical staining, while total APP, phosphorylated-tau protein, CDK5 and PP2A were determined by Western Blotting. Results: (1) Compared to the non-treatment group, the lithium-treatment group had a significantly shorter mean escape latency and a lower proportion of random navigation pattern in the spatial probe test (P<0.05). After the platform was taken away, the rats in the lithium-treatment group crossed the platform quadrant significantly more and stayed longer in the platform quadrant than those in the non-treatment group (P<0.05). (2) The number of Aβ positive neurons in the hippocampus and cortex was significantly less in the lithium-treatment group than in the non-treatment group (P<0.05), but the content of APP was not different between groups (P=0.730). (3) Phosphorylation of tau protein decreased significantly in the lithium-treatment group than that in the non-treatment group (P<0.05). The content of CDK5 in the lithium-treatment group was significantly less than that in the non-treatment group in the cortex and hippocampus, while there was no difference in the content of PP2A between the 2 groups. The expression of CDK5 was significantly correlated with phosphorylated tau (r=0.871, P=0.024) in the lithium-treatment group. Conclusion: Lithium may improve memory function in rats chronically exposed to aluminum by decreasing both the production of Aβ and tau phosphorylation, with the latter results from inhibiting expression of CDK5.展开更多
文摘Objective: To investigate the effects of lithium on cognitive function and metabolism of Amyloid-beta Protein Precursor (APP) and tau phosphorylation in rats chronically exposed to aluminum. Methods: Twenty-four chronically aluminum-exposed rats were randomly divided into 2 groups: a lithium-treatment group and a non-treatment group (n=12 per group). Lithium chloride was administered to the lithium-treatment group via gastric gavage daily for 6 weeks (200 mg/kg·d LiCl), while the non-treatment group was administered the same volume of sodium chloride by the same means. An additional control group (n=12) received no intervention. Memory function was evaluated by the Morris water maze test. Aβ was measured by immunohistochemical staining, while total APP, phosphorylated-tau protein, CDK5 and PP2A were determined by Western Blotting. Results: (1) Compared to the non-treatment group, the lithium-treatment group had a significantly shorter mean escape latency and a lower proportion of random navigation pattern in the spatial probe test (P<0.05). After the platform was taken away, the rats in the lithium-treatment group crossed the platform quadrant significantly more and stayed longer in the platform quadrant than those in the non-treatment group (P<0.05). (2) The number of Aβ positive neurons in the hippocampus and cortex was significantly less in the lithium-treatment group than in the non-treatment group (P<0.05), but the content of APP was not different between groups (P=0.730). (3) Phosphorylation of tau protein decreased significantly in the lithium-treatment group than that in the non-treatment group (P<0.05). The content of CDK5 in the lithium-treatment group was significantly less than that in the non-treatment group in the cortex and hippocampus, while there was no difference in the content of PP2A between the 2 groups. The expression of CDK5 was significantly correlated with phosphorylated tau (r=0.871, P=0.024) in the lithium-treatment group. Conclusion: Lithium may improve memory function in rats chronically exposed to aluminum by decreasing both the production of Aβ and tau phosphorylation, with the latter results from inhibiting expression of CDK5.
