D‐Ser2‐oxyntomodulin ameliorated Aβ31‐35‐induced circadian rhythm disorder in mice. (14th August 2019)

• Record Type: Journal Article
• Authors: Wang, Li; Zhao, Jin; Wang, Chang‐Tu; Hou, Xiao‐Hong; Ning, Na; Sun, Cong; Guo, Shuai; Yuan, Yuan; Li, Lin; Hölscher, Christian; Wang, Xiao‐Hui
• Is Part Of: CNS neuroscience & therapeutics. Volume 26:Number 3(2020)
• Page Start: 343
• Page End: 354
• Publication Date: 2019-08-14
• Subjects: Alzheimer's disease -- Bmal1 -- glucagon‐like peptide‐1 -- Per2; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13211
• Languages: English
• ISSNs: 1755-5930

Abstract

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.