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Article Type

Original Study

Abstract

Background and aim: Alzheimer’s disease (AD) is a common progressivedisease characterized by neurodegeneration. Multiple molecular mechanismssuch as amyloid β (Aβ)formation, tau protein hyperphosphorylation,reducedcholinergic neurotransmission, oxidative stress, and neuroinflammationare involved in the disease pathophysiology. The purpose of thisstudywas to assess potential neuroprotective effect of clopidogrel in ADmodelinduced by aluminum chloride (AlCl3) in ratsMethods: Fortyadult male Sprague-Dawley rats were haphazardly separated into fourgroupsof ten rats each: Control, AlCl3 (100 mg/kg orally), AlCl3 + Memantine(10 mg/kg orally), and AlCl3 + Clopidogrel groups (20 mg/kg orally).AlCl3and drugs were administrated once every day for 42 days. The spatiallearningand memory were evaluated using Morris Water Maze (MWM) test.Aftereuthanization, hippocampal acetylcholinesterase (AChE) activity, tumornecrosis factor alpha (TNF-α),and interleukin-1beta (IL-1β)concentrationswere biochemically assessed in all groups. Moreover, amyloid precursorprotein (APP) mRNA gene expression was analyzed in thehippocampusof all groups with Real-time quantitative polymerase chain reaction(qPCR). Histopathology for amyloid plaques was done in all groups’hippocampususing hematoxylin and eosin and Congo stain.Results: AlCl3 and clopidogrel co-treatment significantly ameliorated thecognitive deficits induced by AlCl3 in rats. Moreover, AlCl3 and clopidogrelco-treatment significantly reduced AChE activity, TNF-α and IL-1β concentrations,and APP mRNA gene expression in the rat hippocampi comparedtoAlCl3-treated rats. AlCl3 and clopidogrel co-treatment significantly reducedTNF-α and IL-1β concentrations in the rat hippocampi compared toAlCl3and memantine co-treated rats. In addition, AlCl3 and clopidogrel cotreatmentalleviated amyloid plaque deposition in the rat hippocampal tissuesstained with hematoxylin and eosin and Congo stains compared toAlCl3-treatedrats.Conclusion:Theseresults showed that clopidogrel could improve cognitivedeficitstriggered by AlCl3 in rats. The neuronal protection influence of clopidogrelin AlCl3-triggered AD might be mediated through its antiinflammatoryeffect as demonstrated by its ability to decrease hippocampalTNF-α and IL-1β concentrations. It might also be mediated through its loweringeffect on AChE activity and/or decreasing mRNA gene expression ofAPPgene in the hippocampus

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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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