الفهرس 
Introduction & Aim of the WorkOnly 14 pages are availabe for public view
 |  | from | 278 |  |  |
| | | from | 278 | | |
Abstract
Introduction and aim of the work: Alzheimer’s disease (AD) is a common progressive neurodegenerative disease. The aim of this study is to evaluate the potential neuroprotective effect of clopidogrel in AD model induced by aluminum chloride (AlCl3) in rats
Materials and Methods: Fifty adult male Sprague-Dawley rats were randomly divided into five groups of ten rats each: Control, AlCl3 (100 mg/kg p.o), AlCl3 + donepezil (5 mg/kg p.o), AlCl3 + Memantine (10 mg/kg p.o), and AlCl3 + Clopidogrel group (20 mg/kg p.o). AlCl3 and the drugs were administrated once daily for 42 days. Learning and memory were assessed using Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. After scarification, hippocampal acetylcholinesterase (AChE) activity, tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1β) concentrations were biochemically assessed in all groups. Moreover, amyloid precursor protein (APP) mRNA gene expression was analyzed in the hippocampus of all groups with Real-time quantitative polymerase chain reaction (qPCR). Histopathology for amyloid plaques was done in all groups using hematoxylin and eosin and Congo stain.
Results: AlCl3 and clopidogrel co-treatment significantly ameliorated the cognitive deficits induced by AlCl3 in rats, significantly reduced AChE activity, TNF-α and IL-1β concentrations, and APP mRNA gene expression in the hippocampus of rats compared to AlCl3-treated rats. AlCl3 and clopidogrel co-treatment significantly reduced TNF-α and IL-1β concentrations in the hippocampus of rats compared to AlCl3 and memantine or donepezil co-treated rats. In addition, AlCl3 and clopidogrel co-treatment alleviated amyloid plaque deposition in the hippocampal tissues of rats compared to AlCl3-treated rats.
Conclusion: Our findings demonstrated for the first time that clopidogrel could alleviate learning and memory impairments induced by AlCl3 in rats. The neuroprotective effect of clopidogrel against AlCl3-induced AD might be mediated mainly through its anti-inflammatory effect as demonstrated by its ability to decrease hippocampal TNF-α and IL-1β concentrations. It might also be mediated through its lowering effect on AChE activity and/or decreasing mRNA gene expression of APP gene in the hippocampus.