کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4313310 1289993 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice
چکیده انگلیسی

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-β peptide (Aβ1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ1–40 or the control peptide Aβ40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ1–40 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 Aβ1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ1–40 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.


► ChE inhibitors are used for therapy of cognitive decline in Alzheimer's disease.
► The effect of BuChE inhibition on Aβ-induced cognitive dysfunction is not clear.
► BuChE or dual BuChE/AChE inhibition improves Aβ-induced cognitive dysfunction.
► BuChE or dual BuChE/AChE inhibition reduced hippocampal protein nitration.
► BuChE inhibition may provide a new strategy for improving cognitive dysfunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 225, Issue 1, 20 November 2011, Pages 222–229
نویسندگان
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