PMID- 30871577
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20200225
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 16
IP  - 1
DP  - 2019 Mar 14
TI  - Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice.
PG  - 62
LID - 10.1186/s12974-019-1450-3 [doi]
LID - 62
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder 
      characterized by an abnormal accumulation of amyloid-beta (Abeta) 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/PS1DeltaE9 (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, Abeta 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 Abeta 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-kappaB 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.
FAU - Gong, Zhuo
AU  - Gong Z
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Huang, Jingyi
AU  - Huang J
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Xu, Biao
AU  - Xu B
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Ou, Zhenri
AU  - Ou Z
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Zhang, Le
AU  - Zhang L
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Lin, Xiaohong
AU  - Lin X
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Ye, Xiujuan
AU  - Ye X
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Kong, Xuejian
AU  - Kong X
AD  - Department of Neurology of the Sixth Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, 511518, China.
FAU - Long, Dahong
AU  - Long D
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Sun, Xiangdong
AU  - Sun X
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - He, Xiaosong
AU  - He X
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Xu, Liping
AU  - Xu L
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Li, Qingqing
AU  - Li Q
AD  - Institute 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 China, 
      Guangzhou, 510260, China.
FAU - Xuan, Aiguo
AU  - Xuan A
AD  - Institute 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 China, 
      Guangzhou, 510260, China. xag2005@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190314
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Coumarins)
RN  - 0 (Cytokines)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one)
SB  - IM
MH  - Alzheimer Disease/complications/genetics
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Brain/drug effects/metabolism/pathology
MH  - Coumarins/*therapeutic use
MH  - Cytokines/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Encephalitis/*drug therapy/etiology
MH  - Female
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Gliosis/drug therapy/genetics
MH  - Maze Learning/drug effects
MH  - Memory Disorders/*drug therapy/etiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurogenesis/drug effects/genetics
MH  - Plaque, Amyloid/drug therapy/etiology
MH  - Presenilin-1/genetics/metabolism
MH  - Signal Transduction/drug effects/genetics
PMC - PMC6417212
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Memory impairment
OT  - Neurogenesis
OT  - Neuroinflammation
OT  - Urolithin A
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All animal studies were performed 
      with the approval by the Ethics Committee of Guangzhou Medical University, 
      Guangdong, China. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: 
      The authors declare that they have no competing interests. PUBLISHER'S NOTE: 
      Springer Nature remains neutral with regard to jurisdictional claims in published 
      maps and institutional affiliations.
EDAT- 2019/03/16 06:00
MHDA- 2019/07/16 06:00
PMCR- 2019/03/14
CRDT- 2019/03/16 06:00
PHST- 2018/11/26 00:00 [received]
PHST- 2019/03/05 00:00 [accepted]
PHST- 2019/03/16 06:00 [entrez]
PHST- 2019/03/16 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2019/03/14 00:00 [pmc-release]
AID - 10.1186/s12974-019-1450-3 [pii]
AID - 1450 [pii]
AID - 10.1186/s12974-019-1450-3 [doi]
PST - epublish
SO  - J Neuroinflammation. 2019 Mar 14;16(1):62. doi: 10.1186/s12974-019-1450-3.