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D-Ser2-oxyntomodulin ameliorated Aβ31-35-induced circadian rhythm disorder in mice.

Authors
  • Wang, Li1
  • Zhao, Jin1
  • Wang, Chang-Tu1, 2
  • Hou, Xiao-Hong1
  • Ning, Na1
  • Sun, Cong1
  • Guo, Shuai1
  • Yuan, Yuan3
  • Li, Lin4
  • Hölscher, Christian5, 6
  • Wang, Xiao-Hui1, 2, 3
  • 1 Department of Pathology, Shanxi Medical University, Taiyuan, China. , (China)
  • 2 Laboratory of Chronobiology, Shanxi Medical University, Taiyuan, China. , (China)
  • 3 Laboratory of Morphology, Department of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China. , (China)
  • 4 Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, China. , (China)
  • 5 Second Hospital, Shanxi Medical University, Taiyuan, China. , (China)
  • 6 Biomedical and Life Science, Faculty of Health and Medicine, Lancaster University, Lancaster, UK.
Type
Published Article
Journal
CNS Neuroscience & Therapeutics
Publisher
Wiley (Blackwell Publishing)
Publication Date
Mar 01, 2020
Volume
26
Issue
3
Pages
343–354
Identifiers
DOI: 10.1111/cns.13211
PMID: 31411808
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The occurrence of circadian rhythm disorder in patients with Alzheimer's disease (AD) is closely related to the abnormal deposition of amyloid-β (Aβ), and d-Ser2-oxyntomodulin (Oxy) is a protease-resistant oxyntomodulin analogue that has been shown to exert neuroprotective effects. This study aimed to explore whether Oxy, a new GLP-1R/GCGR dual receptor agonist, can improve the Aβ-induced disrupted circadian rhythm and the role of GLP-1R. A mouse wheel-running experiment was performed to explore the circadian rhythm, and western blotting and real-time PCR were performed to assess the expression of the circadian clock genes Bmal1 and Per2. Furthermore, a lentivirus encoding an shGLP-1R-GFP-PURO was used to interfere with GLP-1R gene expression and so explore the role of GLP-1R. The present study has confirmed that Oxy could restore Aβ31-35-induced circadian rhythm disorders and improve the abnormal expression of Bmal1 and Per2. After interfering the GLP-1R gene, we found that Oxy could not improve the Aβ31-35-induced circadian rhythm disorder and abnormal expression of clock genes. This study demonstrated that Oxy could improve Aβ31-35-induced circadian rhythm disorders, and GLP-1R plays a critical role. This study thus describes a novel target that may be potentially used in the treatment of AD. © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

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