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

被引：205

作者：

Gong, Zhuo ^{[1
,2
,3
]}

Huang, Jingyi ^{[1
,2
,3
]}

Xu, Biao ^{[1
,2
,3
]}

Ou, Zhenri ^{[1
,2
,3
]}

Zhang, Le ^{[1
,2
,3
]}

Lin, Xiaohong ^{[1
,2
,3
]}

Ye, Xiujuan ^{[1
,2
,3
]}

Kong, Xuejian ^{[4
]}

Long, Dahong ^{[1
,2
,3
]}

Sun, Xiangdong ^{[1
,2
,3
]}

He, Xiaosong ^{[1
,2
,3
]}

Xu, Liping ^{[1
,2
,3
]}

Li, Qingqing ^{[1
,2
,3
]}

Xuan, Aiguo ^{[1
,2
,3
]}

机构：

[1] Guangzhou Med Univ, Affiliated Hosp 2, Inst Neurosci, Key Lab Neurogenet & Channelopathies Guangdong Pr, Guangzhou 510260, Guangdong, Peoples R China

[2] Guangzhou Med Univ, Affiliated Hosp 2, Dept Neurol, Key Lab Neurogenet & Channelopathies Guangdong Pr, Guangzhou 510260, Guangdong, Peoples R China

[3] Minist Educ China, Guangzhou 510260, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Affiliated Hosp 6, Dept Neurol, Guangzhou 511518, Guangdong, Peoples R China

来源：

JOURNAL OF NEUROINFLAMMATION | 2019年 / 16卷 / 1期

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; Urolithin A; Neuroinflammation; Memory impairment; Neurogenesis; NF-KAPPA-B; ACID-DERIVED METABOLITES; BETA PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; ELLAGIC ACID; INDUCED INFLAMMATION; NEURONAL LOSS; IN-VITRO; ELLAGITANNIN METABOLITES; COLONIC METABOLITE;

D O I：

10.1186/s12974-019-1450-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an abnormal accumulation of amyloid- (A) 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/PS1E9 (APP/PS1) mouse model of AD.MethodsMorris 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, A 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.ResultsWe demonstrated that UA ameliorated cognitive impairment, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. Furthermore, UA attenuated A 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-B and P38MAPK, and suppressing Bace1 and APP degradation.ConclusionsOur 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.

引用

页数：13

共 58 条

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