Clopidogrel combats neuroinflammation and enhances learning behavior and memory in a rat model of Alzheimer's disease

Noura El Adle Khalaf, Farida Mohamed El Banna, Mona Younis Youssef, Youssef Mohammed Mosaad, Mohamed-Hesham Yousry Daba, Rehab Hamdy Ashour
Pharmacology, Biochemistry, and Behavior 2020 May 28, : 172956

BACKGROUND AND AIM: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Multiple molecular mechanisms have been employed in its pathogenesis such as Amyloid β (Aβ) formation, tau protein hyperphosphorylation, reduced acetylcholine (ACh) level, and neuroinflammation. This study aimed to assess the possible neuroprotective effect of clopidogrel in AD model induced by aluminum chloride (AlCl3 ) in rats.

METHODS: Sixty adult male Sprague-Dawley rats were divided into four different groups: Control, AlCl3 , AlCl3  + donepezil, and AlCl3  + Clopidogrel. AlCl3 and the drugs were given orally once/day for 42 days. The spatial learning and memory and recognition memory were evaluated using Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests, respectively. After euthanasia, hippocampal acetylcholinesterase (AChE) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) levels were biochemically assessed. Moreover, amyloid precursor protein (APP) mRNA gene expression was analyzed in the hippocampi of all rats. Histopathology for amyloid plaques was done.

RESULTS: Clopidogrel co-treatment significantly ameliorated the cognitive deficits induced by AlCl3 in rats. Besides, clopidogrel significantly reduced AChE activity, TNF-α and IL-1β concentrations, and APP mRNA gene expression in the hippocampi of rats compared to AlCl3 rats. The decrease of hippocampal TNF-α and IL-1β concentrations by clopidogrel was significant compared to donepezil co-treated rats. Clopidogrel co-treatment lessened amyloid plaque deposition in the hippocampal tissues of rats compared to AlCl3 rats.

CONCLUSION: These findings demonstrate that clopidogrel could alleviate learning and memory deficit induced by AlCl3 in rats and significantly reduced AChE activity. The neuroprotective outcome of clopidogrel might be assigned to its anti-inflammatory effect.

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