کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9428856 1615198 2005 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparison of donepezil and memantine for protective effect against amyloid-beta(1-42) toxicity in rat septal neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Comparison of donepezil and memantine for protective effect against amyloid-beta(1-42) toxicity in rat septal neurons
چکیده انگلیسی
Donepezil, a potent acetylcholinesterase (AChE) inhibitor and memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, have been used for the treatment of Alzheimer's disease (AD), and both of them have been shown to have neuroprotective action against glutamate excitotoxicity. However, it is not known whether donepezil and memantine similarly exert neuroprotective effects against amyloid-beta peptide(1-42) [Aβ(1-42)] toxicity in cholinergic neurons. Therefore, in the present study we compared the neuroprotective effects of donepezil and memantine against Aβ(1-42) toxicity in rat cultured septal cholinergic neurons, because deficit in cholinergic neurotransmission is a major feature in AD, and medial septal cholinergic neurons are known to degenerate in AD patients. Septal neuronal cells were cultured for 7 days and then 5 μmol/L of Aβ(1-42) was added to the medium for 48 h. Measurement of the efflux of lactate dehydrogenase (LDH) indicated that septal neuronal cells were highly susceptible to Aβ toxicity and relatively resistant to NMDA toxicity. Donepezil concentration-dependently reduced the LDH efflux induced by Aβ(1-42), and the effect was significant at 1 μmol/L and above. NMDA receptor antagonists, memantine and MK-801, did not show a significant neuroprotective effect against Aβ(1-42) toxicity. It is concluded that the neuroprotective effect of donepezil against Aβ(1-42) toxicity is not mediated by interference with the NMDA-mediated excitotoxic process, and that donepezil may be more effective than memantine against cholinergic neuronal damage induced by Aβ(1-42) exposure.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 391, Issues 1–2, 31 December 2005, Pages 17-21
نویسندگان
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