Effects of lithium on CDK5 and PP2A expressions in chronic aluminum exposure rats

Objective: To explore the effects of lithium on expressions of cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in the brains of chronic aluminum exposure rats so as to further understand the mechanism of lithium's inhibition on tau phosphorylation. Methods: We divided 12 chronic aluminum chloride exposure rats into treatment group and non-treatment group (6 rats in each). Treatment group was given lithium chloride (200 mg/kg·d) via gastric perfusion daily for 6 weeks, while the non-treatment group sodium chloride at the same dosage and the normal group (6 non-aluminum exposure rats of the same month old) without intervention. Six weeks later, all the rats received Morris water maze test for learning memory function; CDK5 and PP2A expressions and phosphorylated tau protein level in rat hippocampus were determined by Western blotting. Results: Compared with normal group, non-treatment of chronic aluminum exposure group showed higher phosphorylated tau protein level and CDK5 expression in the brain (P<0.05), and the level of phosphorylated tau had a significantly positive correlation with CDK5 expression Cr = 0.702, P = 0.036). After 6 weeks' treatment with lithium, phosphorylated tau protein and CDK5 expression decreased significantly in the brain compared with those in non-treatment group (P<0.01). Moreover, phosphorylated tau had a significantly positive correlation with the expression of CDK5 (r = 0.871, P = 0.024) in lithium treatment group. There was no significant difference in PP2A expression among treatment group, non-treatment group and normal group (P>0.05). Conclusion: Lithium may reduce tau phosphorylation and neurofibrillary tangle formation by inhibiting the expression of CDK5.