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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Alzheimer's Disease | Research

Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice

Authors: Zhuo Gong, Jingyi Huang, Biao Xu, Zhenri Ou, Le Zhang, Xiaohong Lin, Xiujuan Ye, Xuejian Kong, Dahong Long, Xiangdong Sun, Xiaosong He, Liping Xu, Qingqing Li, Aiguo Xuan

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by an abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and impaired neurogenesis. Urolithin A (UA), a gut-microbial metabolite of ellagic acid, has been reported to exert anti-inflammatory effects in the brain. However, it is unknown whether UA exerts its properties of anti-inflammation and neuronal protection in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD.

Methods

Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia, Aβ deposition, and neurogenesis. The expression of inflammatory mediators were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The modulating effects of UA on cell signaling pathways were assayed by Western blotting.

Results

We demonstrated that UA ameliorated cognitive impairment, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. Furthermore, UA attenuated Aβ deposition and peri-plaque microgliosis and astrocytosis in the cortex and hippocampus. We also found that UA affected critical cell signaling pathways, specifically by enhancing cerebral AMPK activation, decreasing the activation of P65NF-κB and P38MAPK, and suppressing Bace1 and APP degradation.

Conclusions

Our results indicated that UA imparted cognitive protection by protecting neurons from death and triggering neurogenesis via anti-inflammatory signaling in APP/PS1 mice, suggesting that UA might be a promising therapeutic drug to treat AD.
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Metadata
Title
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice
Authors
Zhuo Gong
Jingyi Huang
Biao Xu
Zhenri Ou
Le Zhang
Xiaohong Lin
Xiujuan Ye
Xuejian Kong
Dahong Long
Xiangdong Sun
Xiaosong He
Liping Xu
Qingqing Li
Aiguo Xuan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1450-3

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