کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5828942 | 1558983 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
 amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease](/preview/png/5828942.png)
چکیده انگلیسی
Alzheimer's disease pathomimetic toxicity could be induced in mice within one week after the intracerebroventricular (i.c.v.) injection of an aggregated preparation of the highly toxic and endogenous amyloid-β fragment Aβ25-35. It was recently reported that Aβ25-35 also provokes a modification of APP processing with accumulation of endogenous Aβ1-42. We here analyzed whether a γ-secretase inhibitor, BMS-299897, attenuated this Aβ25-35-induced Aβ1-42 seeding and toxicity. The compound was administered at 0.1-1 nmol/mouse, concomittantly with Aβ25-35 (9 nmol) in male Swiss mice. After one week, the contents in Aβ1-42 and Aβ1-40, and the levels in lipid peroxidation were analyzed in the mouse hippocampus. Mice were submitted to spontaneous alternation, passive avoidance and object recognition to analyze their short- and long-term memory abilities. Aβ25-35 increased Aβ1-42 content (+240%) but failed to affect Aβ1-40. BMS-299897 blocked the increase in Aβ1-42 content and decreased Aβ1-40 levels significantly. The compound did not affect Aβ25-35-induced increase in hippocampal lipid peroxidation. Behaviorally, BMS-299897 blocked the Aβ25-35-induced deficits in spontaneous alternation or novel object recognition, using a 1 h intertrial time interval. BMS-299896 failed to affect the passive avoidance impairments or novel object recognition, using a 24 h intertrial time interval. These results confirmed that Aβ25-35 injection provoked an accumulation in endogenous Aβ1-42, an effect blocked by γ-secretase inhibition. This Aβ1-42 accumulation marginally contributed to the toxicity or long-term memory deficits. However, since the seeded Aβ1-42 affected short-term memory, the rapid Aβ25-35 injection Alzheimer's disease model could be used to screen the activity of new secretase inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 698, Issues 1â3, 5 January 2013, Pages 193-199
Journal: European Journal of Pharmacology - Volume 698, Issues 1â3, 5 January 2013, Pages 193-199
نویسندگان
Johann Meunier, Vanessa Villard, Laurent Givalois, Tangui Maurice,