Role of Kenpaullone in improving memory function and its molecular mechanism in Alzheimer's disease rats

Abstract

Objective To investigate the effect of Kenpaullone on memory dysfunction in Alzheimer's disease (AD) model rats and its possible mechanism. Methods Twenty healthy male SD rats were divided into control group, model group, low dose group and high-dose group by random number table method (n=5). The rats in the control group did not receive any treatment; 2 μL 0.5 mol/L wortmannin was injected into the hippocampal area of rats in the later three groups via stereotaxic method; The rats in the high-dose and low-dose groups were further injected with 5 μL 1 mmol/L and 5 μL 0.5 mmol/L Kenpaullone 24 h after wortmannin injection. Three weeks after Kenpaullone injection, the memory functions of rats in each group were measured by water maze. The expressions of cyclin-dependent kinase-5 (CDK5)/p25, glycogen synthase kinase-3β (GSK3β) and phosphorylated tau (p-tau) in the hippocampal CA3 regions were determined by immunohistochemistry. Synapsin I expression was detected by Western blotting. Results (1) In the water maze experiment: as compared with those in the model group, the incubation periods of rats in the high-dose and low-dose groups were significantly shortened (P<0.05); as compared with those in the model group and the low-dose group, the times of crossing the platform and the retention time in the high-dose group were significantly increased (P<0.05). (2) In immunohistochemical staining, as compared with the model group, the high-dose group had significantly decreased CDK5, GSK-3β, and p-tau expressions (P<0.05). (3) Western blotting indicated that as compared with that in the model group, synapasin I expression was significantly increased in the high-dose group (P<0.05). Conclusion Kenpaullone can decrease the GSK-3β, CDK5/p25 and p-tau protein expressions and increase synapsin I protein expression in the hippocampus CA3 region, and improve cognitive dysfunction of the rats. Key words: Alzheimer's disease; Kenpaullone; Glycogensynthase kinase-3; Cyclin-dependent kinase-5; Phosphorylated tau protein; Synapsin I