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Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia

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Abstract

Alzheimer's disease, characterized by neuroinflammation and beta-amyloid protein plaques, is a memory-threatening neurodegenerative disease with no effective treatment. Here, the effect of bilberry anthocyanins (BA) on cognitive functions was evaluated using APP/PSEN1 transgenic Alzheimer's disease model mice and their WT littermates. Our results revealed that BA appreciably improves learning and memory abilities and reverses defects to cognitive functions in APP/PSEN1 mice. Furthermore, BA reverses brain, liver and kidney damage caused by Alzheimer's disease, with no significant changes in oxidative stress and lipid metabolism-related indicators. In addition, BA decreases serum and brain lipopolysaccharide (LPS) levels and increases fecal short-chain fatty acid content. Immunofluorescence and RT-PCR analysis results showed that BA fully activates the microglia and astrocytes, downregulates the expression of inflammatory factors (TNF-α, NF-Kβ, IL-1β, IL-6, COX-2, iNOS and CD33) and chemokine receptor CX3CR1, and upregulates the expression of microglia homeostatic factors (TREM2 and TYROBP) and Toll-like receptors (TLR2 and TLR4). Moreover, western blot analysis revealed that BA significantly upregulates the expression of synaptic and phagocytotic function-related proteins (CD68, synaptophysin and IRF7) in APP/PSEN1 mice. Altogether, we show for the first time that BA consumption reverses Alzheimer's disease-induced cognitive disfunction, decreases hippocampal neuroinflammatory responses, and induces phagocytosis of microglia to beta-amyloid protein plaques by regulating the CD33/TREM2/TYROBP signaling pathway in microglia.

Graphical abstract: Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia

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Article information


Submitted
10 Sep 2019
Accepted
06 Jan 2020
First published
07 Jan 2020

Food Funct., 2020, Advance Article
Article type
Paper

Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia

J. Li, R. Zhao, Y. Jiang, Y. Xu, H. Zhao, X. Lyu and T. Wu, Food Funct., 2020, Advance Article , DOI: 10.1039/C9FO02103E

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