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Urolithin A Attenuates Memory Impairment and Neuroinflammation in APP/PS1 Mice

Urolithin A Attenuates Memory Impairment and Neuroinflammation in APP/PS1 Mice

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

J Neuroinflammation. 2019 Mar 14;16(1):62.

PMID: 30871577

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1143700	Urolithin A		1143-70-0	Price

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