Lithium improves memory by decreasing A-beta production and tau phosphorylation in rats chronically exposed to aluminum  

作　　者：Cao Hongmei Qu Qiumin Lu Wenhui Kang Li Yang Xiaobo 

机构地区：[1]Department of Neurology, First Affiliated Hospital, Xi 'an Jiaotong University, Xi'an 710061, China

出　　处：《Journal of Medical Colleges of PLA(China)》2009年第6期311-320,共10页中国人民解放军军医大学学报（英文版）

摘　　要：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 chronObjective： 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

关 键 词：DEMENTIA LITHIUM Amyloid beta-protein Tau phosphorylation 

分 类 号：Q95-337[生物学—动物学] S311[农业科学—作物栽培与耕作技术]