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

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.

• Authors: Li Wang, Jin Zhao, Chang-Tu Wang, Xiao-Hong Hou, Na Ning, Cong Sun, Shuai Guo, Yuan Yuan, Lin Li, Christian Hölscher, Xiao-Hui Wang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 26 Issue 3 Pg. 343-354 (03 2020) ISSN: 1755-5949 [Electronic] England
• PMID: 31411808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Chemical References

• ARNTL Transcription Factors
• Amyloid beta-Peptides
• Arntl protein, mouse
• D-Ser2-oxyntomodulin
• Glp1r protein, mouse
• Glucagon-Like Peptide-1 Receptor
• Oxyntomodulin
• Peptide Fragments
• Per2 protein, mouse
• Period Circadian Proteins
• amyloid beta-protein (31-35)

Topics

• ARNTL Transcription Factors (biosynthesis)
• Amyloid beta-Peptides (toxicity)
• Animals
• Cell Line
• Chronobiology Disorders (chemically induced, drug therapy, metabolism)
• Glucagon-Like Peptide-1 Receptor (biosynthesis)
• Male
• Mice
• Mice, Inbred C57BL
• Oxyntomodulin (therapeutic use)
• Peptide Fragments (toxicity)
• Period Circadian Proteins (biosynthesis)