Wang, L. and Zhao, J. and Wang, C.-T. and Hou, X.-H. and Ning, N. and Sun, C. and Guo, S. and Yuan, Y. and Li, L. and Hölscher, C. and Wang, X.-H. (2020) D-Ser2-oxyntomodulin ameliorated Aβ31-35-induced circadian rhythm disorder in mice. CNS Neuroscience and Therapeutics, 26 (3). pp. 343-354.
Full text not available from this repository.Abstract
Introduction: 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. Aims: 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. Methods: 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. Results: 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. Conclusion: 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.