Effect of donepezil hydrochloride on the Calpain I-Cdk5 pathway expression in the hippocampus of mice with vascular dementia

Abstract

Objective To investigate the effect of donepezil hydrochloride on the expression of Calpain I-Cdk5/p25 pathway in the hippocampal CA1 area by cerebral ischemia and reperfusion in mice. Methods Mice were divided into model group, sham-operated group and donepezil-treated group. The expression of Calpain I in hippocampal CA1 area was measured by immunohistochemistry staining respectively at 4, 6 and 8 weeks post cerebral ischemia and reperfusion. Western blot was used to evaluate Cdk5 and p25 protein expression. Results The abilities of learning and memory performance was damaged significantly at 4, 6 and 8 weeks after surgery compared to sham-operated group (P<0.05). The expression of Calpain I of model group were (0.098±0.009), (0.129±0.01), (0.116±0.01), which were higher than that of sham-operated group (0.03±0.003), (0.031±0.003), (0.029±0.003)and there was significant difference (P<0.05). The expression of Cdk5 in model group was (0.54±0.05), (0.73±0.07), (0.7±0.06), which were higher than that of sham-operated group(0.23±0.02), (0.31±0.02), (0.33±0.02)and there was significant difference (P<0.05). The expression of p25 in model group was (0.44±0.04), (0.51±0.04), (0.55±0.06), which were higher than that of sham-operated group(0.19±0.02), (0.24±0.02), (0.2±0.02)and there was significant difference(P<0.05). The expression of Calpain I of donepezil-treated group was (0.041±0.004), (0.054±0.004), (0.046±0.003), which were lower than that of model group. The expression of Cdk5 was(0.28±0.02), (0.33±0.03), (0.38±0.02), and expression of p25 was (0.26±0.02), (0.25±0.03), (0.21±0.02), which were lower than that of model group respectively(P<0.05). Conclusion Donepezil hydrochloride probably improve the learning and memory abilities by reducing the expression of Calpain I and Cdk5/p25. Key words: Vascular dementia; Donepezi1 hydrochloride; Calpain I; Cdk5