2008Zhongguo laonianxue zazhiRequires access

The effect of donepezil hydrochloride on the changes of ERK2 and p-ERK in hippocampus of mice with vascular dementia

Xue Wang

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Abstract

Objective To observe the effect of donepezil hydrochloride on the changes of extracellular signal-regulated kinase(ERK2 and p-ERK) in hippocampus of mice with vascular dementia(VD).Methods Kunming mice were divided into sham,model and treatment group with donepezil hydrochloride randomly.The models of VD mice were established through three times ischemia-reperfusion of bilateral common carotid arteries.The behavioral scores of three groups were investigated by step-down test and water maze test at days 29,30 respectively.The expressing changes of ERK2 in hippocampus CA1 and p-ERK in hippocampus CA3 were observed by immunohistochemistry technique.Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride(P0.05).The number of positive ERK1 neurons 〔(16.17±0.75) vs(23.17±1.08),P0.05〕 was less,the average optical of positive neurons was also lower 〔(0.208 3±0.004 8) vs(0.240 0±0.005 8),P0.05〕 in hippocampus CA1 of model group than that in sham group.The average optical of positive p-ERK in hippocampus CA3 was lower than that in sham group 〔(0.186 7±0.008 4) vs(0.271 7±0.012 2) ;P0.05〕.However,there was no significant difference between sham and treatment group(P0.05).Conclusions The decreased expression of ERK2 and p-ERK in hippocampal neurons may participate in the pathogenesis of VD.Donepezil hydrochloride could increase the content of acetylcholine which could activate ERK through M receptor and furthermore improve abilities of learning and memory.

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Objective To observe the effect of donepezil hydrochloride on the changes of extracellular signal-regulated kinase(ERK2 and p-ERK) in hippocampus of mice with vascular dementia(VD).Methods Kunming mice were divided into sham,model and treatment group with donepezil hydrochloride randomly.The models of VD mice were established through three times ischemia-reperfusion of bilateral common carotid arteries.The behavioral scores of three groups were investigated by step-down test and water maze test at days 29,30 respectively.The expressing changes of ERK2 in hippocampus CA1 and p-ERK in hippocampus CA3 were observed by immunohistochemistry technique.Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride(P0.05).The number of positive ERK1 neurons 〔(16.17±0.75) vs(23.17±1.08),P0.05〕 was less,the average optical of positive neurons was also lower 〔(0.208 3±0.004 8) vs(0.240 0±0.005 8),P0.05〕 in hippocampus CA1 of model group than that in sham group.The average optical of positive p-ERK in hippocampus CA3 was lower than that in sham group 〔(0.186 7±0.008 4) vs(0.271 7±0.012 2) ;P0.05〕.However,there was no significant difference between sham and treatment group(P0.05).Conclusions The decreased expression of ERK2 and p-ERK in hippocampal neurons may participate in the pathogenesis of VD.Donepezil hydrochloride could increase the content of acetylcholine which could activate ERK through M receptor and furthermore improve abilities of learning and memory.

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Available abstract

Objective To observe the effect of donepezil hydrochloride on the changes of extracellular signal-regulated kinase(ERK2 and p-ERK) in hippocampus of mice with vascular dementia(VD).Methods Kunming mice were divided into sham,model and treatment group with donepezil hydrochloride randomly.The models of VD mice were established through three times ischemia-reperfusion of bilateral common carotid arteries.The behavioral scores of three groups were investigated by step-down test and water maze test at days 29,30 respectively.The expressing changes of ERK2 in hippocampus CA1 and p-ERK in hippocampus CA3 were observed by immunohistochemistry technique.Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride(P0.05).The number of positive ERK1 neurons 〔(16.17±0.75) vs(23.17±1.08),P0.05〕 was less,the average optical of positive neurons was also lower 〔(0.208 3±0.004 8) vs(0.240 0±0.005 8),P0.05〕 in hippocampus CA1 of model group than that in sham group.The average optical of positive p-ERK in hippocampus CA3 was lower than that in sham group 〔(0.186 7±0.008 4) vs(0.271 7±0.012 2) ;P0.05〕.However,there was no significant difference between sham and treatment group(P0.05).Conclusions The decreased expression of ERK2 and p-ERK in hippocampal neurons may participate in the pathogenesis of VD.Donepezil hydrochloride could increase the content of acetylcholine which could activate ERK through M receptor and furthermore improve abilities of learning and memory.

Key concepts: Hippocampus, Donepezil, Vascular dementia, Hippocampal formation, MAPK/ERK pathway, Internal medicine, Morris water navigation task, Medicine

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