Background and aim: Alzheimer's disease (AD) is a common progressive
disease characterized by neurodegeneration. Multiple molecular mechanisms
such as amyloid β (Aβ
)
formation, tau protein hyperphosphorylation,
reduced
cholinergic neurotransmission, oxidative stress, and neuroinflammation
are involved in the disease pathophysiology. The purpose of this
study
was to assess potential neuroprotective effect of clopidogrel in AD
model
induced by aluminum chloride (AlCl3) in rats
Methods: Forty
adult male Sprague-Dawley rats were haphazardly separated into four
groups
of ten rats each: Control, AlCl3 (100 mg/kg orally), AlCl3 + Memantine
(10 mg/kg orally), and AlCl3 + Clopidogrel groups (20 mg/kg orally).
AlCl3
and drugs were administrated once every day for 42 days. The spatial
learning
and memory were evaluated using Morris Water Maze (MWM) test.
After
euthanization, 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'
hippocampus
using hematoxylin and eosin and Congo stain.
Results: AlCl
3
and clopidogrel co-treatment significantly ameliorated the
cognitive deficits induced by AlCl3 in rats. Moreover, AlCl3 and clopidogrel
co-treatment significantly reduced AChE activity, TNF-α and IL-1β concentrations,
and APP mRNA gene expression in the rat hippocampi compared
to
AlCl3-treated rats. AlCl3 and clopidogrel co-treatment significantly reduced
TNF-α and IL-1β concentrations in the rat hippocampi compared to
AlCl3
and memantine co-treated rats. In addition, AlCl3 and clopidogrel cotreatment
alleviated amyloid plaque deposition in the rat hippocampal tissues
stained with hematoxylin and eosin and Congo stains compared to
AlCl3-treated
rats.
Conclusion:
These
results showed that clopidogrel could improve cognitive
deficits
triggered by AlCl3 in rats. The neuronal protection influence of clopidogrel
in AlCl3-triggered AD might be mediated through its antiinflammatory
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