Naproxen as a potential candidate for promoting rivastigmine anti-Alzheimer activity against aluminum chloride-prompted Alzheimer's-like disease in rats; neurogenesis and apoptosis modulation as a possible underlying mechanism
Year: 2021
Type: article
Abstract: Alzheimer’s disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. Neuroinflammation plays a central role in AD pathogenesis. We tested the hypothesis that naproxen, a non-steroidal anti-inflammatory drug (NSAID), administration to the rivastigmine-treated aluminum chloride (AlCl3), Alzheimer's rat model, could provide an additive neuroprotective effect compared to rivastigmine alone. The studied groups were control (Cont), AlCl3 treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats’ memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. A marker of astroglial injury; glial fibrillary acidic protein (GFAP), the apoptosis maker; activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity, massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Rivastigmine, naproxen, and their combination decreased hippocampal AChE activity, mitigated behavioral and neuropathological changes in Al-intoxicated rats, possibly through downregulation of activated caspase-3 and upregulation of nestin. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. Naproxen's efficacy was demonstrated by its ability to act at the cellular level, enhance neurogenesis, and suppress apoptosis without having an additional mitigating impact in Al-induced cognitive impairment.
Source: European Journal of Pharmacology
Institution: Assiut University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4200419876