Furukawa-Hibi_2011_Behav.Brain.Res_225_222

Reference

Title : Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-beta peptide in mice - Furukawa-Hibi_2011_Behav.Brain.Res_225_222
Author(s) : Furukawa-Hibi Y , Alkam T , Nitta A , Matsuyama A , Mizoguchi H , Suzuki K , Moussaoui S , Yu QS , Greig NH , Nagai T , Yamada K
Ref : Behavioural Brain Research , 225 :222 , 2011
Abstract :

The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethyl-norcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-beta peptide (Abeta(1-40)) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Abeta(1-40) or the control peptide Abeta(40-1) on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0mg/kg), rivastigmine (0.03, 0.1, 0.3mg/kg) or PEC (1.0, 3.0mg/kg) 20min prior to, or immediately after the acquisition session (Day 4) ameliorated the Abeta(1-40) induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0-3 inclusively, ameliorated the cognitive dysfunction in Abeta(1-40) challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Abeta(1-40) induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD.

PubMedSearch : Furukawa-Hibi_2011_Behav.Brain.Res_225_222
PubMedID: 21820013

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Citations formats

Furukawa-Hibi Y, Alkam T, Nitta A, Matsuyama A, Mizoguchi H, Suzuki K, Moussaoui S, Yu QS, Greig NH, Nagai T, Yamada K (2011)
Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-beta peptide in mice
Behavioural Brain Research 225 :222

Furukawa-Hibi Y, Alkam T, Nitta A, Matsuyama A, Mizoguchi H, Suzuki K, Moussaoui S, Yu QS, Greig NH, Nagai T, Yamada K (2011)
Behavioural Brain Research 225 :222