Nagakura_2013_Eur.J.Pharmacol_703_53

Reference

Title : Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine - Nagakura_2013_Eur.J.Pharmacol_703_53
Author(s) : Nagakura A , Shitaka Y , Yarimizu J , Matsuoka N
Ref : European Journal of Pharmacology , 703 :53 , 2013
Abstract :

Alzheimer's disease is characterized by a progressive decline in cognitive function and involves beta-amyloid (Abeta) in its pathogenesis. To characterize cognitive deficits associated with Abeta accumulation, we analyzed PS1/APP mice overexpressing mutant presenilin-1 (PS1, M146L; line 6.2) and amyloid precursor protein (APP, K670N/M671L; line Tg2576), a mouse model of Alzheimer's disease with accelerated Abeta production. Age-dependent changes in working and spatial memory behaviors were investigated using Y-maze and Morris water maze tasks, respectively, in female PS1/APP mice at ages of 2, 4, 6, and 12 months. Significant deficits in working and spatial memory were observed from 4 and 6 months of age, respectively. Acute single-dose administrations of memantine, a low-to-moderate-affinity N-methyl-d-aspartate (NMDA) antagonist, showed improvements in working memory deficits at 4 months of age, whereas donepezil, an acetylcholinesterase (AChE) inhibitor, did not. However, both drugs improved spatial memory dysfunction at 6 months of age at therapeutically relevant doses. No age-related dramatic changes were observed in expression levels of several proteins relating to memory dysfunction and also the mechanisms of donepezil and memantine in the cerebral cortex of PS1/APP mice until 6 months of age. Taken together, these results suggest dysfunctions in cholinergic and/or glutamatergic transmissions may be involved in the cognitive deficits associated with Abeta toxicity. Since donepezil and memantine have been widely used for treating patients of Alzheimer's disease, these results also suggest that cognitive deficits in PS1/APP mice assessed in the Y-maze and Morris water maze tasks are a useful animal model for evaluating novel Alzheimer's disease therapeutics.

PubMedSearch : Nagakura_2013_Eur.J.Pharmacol_703_53
PubMedID: 23276665

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Citations formats

Nagakura A, Shitaka Y, Yarimizu J, Matsuoka N (2013)
Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine
European Journal of Pharmacology 703 :53

Nagakura A, Shitaka Y, Yarimizu J, Matsuoka N (2013)
European Journal of Pharmacology 703 :53