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The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice.

ABSTRACT: Alzheimer's disease (AD) is the most common senile dementia in the world. Although important progress has been made in understanding the pathogenesis of AD, current therapeutic approaches provide only modest symptomatic relief. In this study, we evaluated the neuroprotective effect of quercetin (25 mg/kg) administration via i.p. injection every 48 h for 3 months on aged (21-24 months old) triple transgenic AD model (3xTg-AD) mice. Our data show that quercetin decreases extracellular ?-amyloidosis, tauopathy, astrogliosis and microgliosis in the hippocampus and the amygdala. These results were supported by a significant reduction in the paired helical filament (PHF), ?-amyloid (?A) 1-40 and ?A 1-42 levels and a decrease in BACE1-mediated cleavage of APP (into CTF?). Additionally, quercetin induced improved performance on learning and spatial memory tasks and greater risk assessment behavior based on the elevated plus maze test. Together, these findings suggest that quercetin reverses histological hallmarks of AD and protects cognitive and emotional function in aged 3xTg-AD mice.

SUBMITTER: Sabogal-Guaqueta AM

PROVIDER: S-EPMC4387064 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice.

Sabogal-Guáqueta Angélica Maria AM Muñoz-Manco Juan Ignacio JI Ramírez-Pineda Jose R JR Lamprea-Rodriguez Marisol M Osorio Edison E Cardona-Gómez Gloria Patricia GP

Neuropharmacology 20150207

Alzheimer's disease (AD) is the most common senile dementia in the world. Although important progress has been made in understanding the pathogenesis of AD, current therapeutic approaches provide only modest symptomatic relief. In this study, we evaluated the neuroprotective effect of quercetin (25 mg/kg) administration via i.p. injection every 48 h for 3 months on aged (21-24 months old) triple transgenic AD model (3xTg-AD) mice. Our data show that quercetin decreases extracellular β-amyloidosi ...[more]

PMID: 25666032

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Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disease manifested by cognitive impairment. As a unique approach to open the blood-brain barrier (BBB) noninvasively and temporarily, a growing number of studies showed that low-intensity focused ultrasound in combination with microbubbles (FUS/MB), in the absence of therapeutic agents, is capable of ameliorating amyloid or tau pathology, concurrent with improving memory deficits of AD animal models. However, the effects of FUS/MB on both the two pathologies simultaneously, as well as the memory behaviors, have not been reported so far. Methods: In this study, female triple transgenic AD (3×Tg-AD) mice at eight months of age with both amyloid-? (A?) deposits and tau phosphorylation were treated by repeated FUS/MB in the unilateral hippocampus twice per week for six weeks. The memory behaviors were investigated by the Y maze, the Morris water maze and the step-down passive avoidance test following repeated FUS/MB treatments. Afterwards, the involvement of A? and tau pathology were assessed by immunohistochemical analysis. Neuronal health and phagocytosis of A? deposits by microglia in the hippocampus were examined by confocal microscopy. Further, hippocampal proteomic alterations were analyzed by employing two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with mass spectrometry. Results: The three independent memory tasks were indicative of evident learning and memory impairments in eight-month-old 3×Tg-AD mice, which developed intraneuronal A?, extracellular diffuse A? deposits and phosphorylated tau in the hippocampus and amygdala. Following repeated FUS/MB treatments, significant improvement in learning and memory ability of the 3×Tg-AD mice was achieved. Amelioration in both A? deposits and phosphorylated tau in the sonicated hemisphere was induced in FUS/MB-treated 3×Tg-AD mice. Albeit without increase in neuron density, enhancement in axonal neurofilaments emerged from the FUS/MB treatment. Confocal microscopy revealed activated microglia engulfing A? deposits in the FUS/MB-treated hippocampus. Further, proteomic analysis revealed 20 differentially expressed proteins, associated with glycolysis, neuron projection, mitochondrial pathways, metabolic process and ubiquitin binding etc., in the hippocampus between FUS/MB-treated and sham-treated 3×Tg-AD mice. Conclusions: Our findings reinforce the positive therapeutic effects on AD models with both A? and tau pathology induced by FUS/MB-mediated BBB opening, further supporting the potential of this treatment regime for clinical applications.

Dataset Information

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice.

Publications

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice.

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