Abstract
Alzheimer's disease typically presents with impaired cognition and pathological morphologic changes, including the accumulation of amyloid-β plaques. Disease-modifying drugs are in urgent need as neuroprotective therapies. Exploration of novel therapeutics for alleviating symptoms of Alzheimer's disease has found promise in plant extracts of functional phenols. Paeonol is a water-soluble phenolic substance that has been shown to confer diverse biological effects, including neuroprotection. An Alzheimer's disease model of APP/PS1 double transgenic mice was used in this study, and the therapeutic effects of paeonol were assessed after three weeks' administration. It was found that paeonol treatment significantly increased behavioral performance in the Morris water maze test and increased discrimination rate in the novel object recognition test compared to vehicle-treated APP/PS1 mice. Histologically, paeonol treatment significantly alleviated the Aβ plaque burden, reduced neural loss, inhibited microglia activation, and decreased neuroinflammation in the brain of APP/PS1 mice. In addition, a number of Alzheimer's disease-related synaptic plasticity deficits were ameliorated. The present results indicate that paeonol significantly relieved amyloid-β deposition and amyloid-β -mediated neuropathology in the brain of APP/PS1 mice, suggesting the potential of paeonol as a preventive and therapeutic agent for Alzheimer's disease.
Highlights
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders characterized by impairments of cognitive function [1]
In the Morris water maze (MWM), the results showed that the paeonol treated APP/PS1 mice took less time to reach the hidden platform than the vehicle-treated APP/PS1 mice during the training phase (Fig. 1A,B)
In the Novel object recognition (NOR) test, as expected, vehicle-APP/PS1 mice could not distinguish the novel from the familiar object, while paeonol-treat APP/PS1 mice displayed a significantly higher discrimination index, with better cognitive performance (Fig. 1E,F)
Summary
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders characterized by impairments of cognitive function [1]. The dominant pathological hallmarks of AD include aggregated amyloid-β (Aβ) peptides that form plaques, activating neuroinflammation and neuronal damage, which contribute to impaired cognitive function. Pathophysiological studies suggest that Aβ deposited throughout the brain plays a primary pathogenic role in AD [2]. A number of studies suggest that Aβ deposited throughout the cortex and hippocampus contribute to the pathophysiology AD [4]. The APP/PS1 mouse is widely used in preclinical AD studies for its close connection with Aβ pathology. The presence of Aβ peptides is considered to have the secondary role of triggering microglial aggregation [7], with microglial activation amplifying neuroinflammation, producing reactive oxidative species and inflammatory cytokines (TNF-α, IL1β) [8], which contribute to furthering neurodegeneration in AD. Though activated microglia have a beneficial role in Aβ clearance, chronic inflammation is detrimental and may lead to a dysregulated, irreversible inflammatory feedforward loop [9]
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