Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice
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-in...
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Format: | Article |
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BMC
2019-03-01
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Series: | Journal of Neuroinflammation |
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Online Access: | http://link.springer.com/article/10.1186/s12974-019-1450-3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice Journal of Neuroinflammation Alzheimer’s disease Urolithin A Neuroinflammation Memory impairment Neurogenesis |
author_facet |
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 |
author_sort |
Zhuo Gong |
title |
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice |
title_short |
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice |
title_full |
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice |
title_fullStr |
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice |
title_full_unstemmed |
Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice |
title_sort |
urolithin a attenuates memory impairment and neuroinflammation in app/ps1 mice |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2019-03-01 |
description |
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. |
topic |
Alzheimer’s disease Urolithin A Neuroinflammation Memory impairment Neurogenesis |
url |
http://link.springer.com/article/10.1186/s12974-019-1450-3 |
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doaj-b0c99ea370e64368b59421d4f2a0b91e2020-11-25T02:09:19ZengBMCJournal of Neuroinflammation1742-20942019-03-0116111310.1186/s12974-019-1450-3Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 miceZhuo Gong0Jingyi Huang1Biao Xu2Zhenri Ou3Le Zhang4Xiaohong Lin5Xiujuan Ye6Xuejian Kong7Dahong Long8Xiangdong Sun9Xiaosong He10Liping Xu11Qingqing Li12Aiguo Xuan13Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaDepartment of Neurology of the Sixth Affiliated Hospital, Guangzhou Medical UniversityInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaInstitute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaAbstract 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.http://link.springer.com/article/10.1186/s12974-019-1450-3Alzheimer’s diseaseUrolithin ANeuroinflammationMemory impairmentNeurogenesis |