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Updated: Jan 20, 2026

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents
05:46

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

Published on: January 24, 2013

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

Li Wang1, Jin Zhao1, Chang-Tu Wang1,2

  • 1Department of Pathology, Shanxi Medical University, Taiyuan, China.

CNS Neuroscience & Therapeutics
|August 15, 2019
PubMed
Abstract

Insights

The novel compound Oxy restores circadian rhythm disrupted by amyloid-beta in Alzheimer's disease models. This effect is mediated through the GLP-1 receptor, suggesting a new therapeutic target for AD.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Pharmacology

Background:

  • Alzheimer's disease (AD) is linked to circadian rhythm disorders, often associated with amyloid-beta (Aβ) deposition.
  • Oxy (d-Ser2-oxyntomodulin) is a neuroprotective, protease-resistant oxyntomodulin analogue.

Purpose of the Study:

  • To investigate if Oxy, a GLP-1R/GCGR dual agonist, can ameliorate Aβ-induced circadian rhythm disruption.
  • To elucidate the role of the Glucagon-Like Peptide-1 Receptor (GLP-1R) in this process.

Main Methods:

  • Mouse wheel-running experiments assessed circadian rhythm.
  • Western blotting and real-time PCR analyzed circadian clock gene expression (Bmal1, Per2).
  • Gene silencing of GLP-1R using lentivirus explored its functional significance.

Main Results:

  • Oxy successfully restored circadian rhythm and normalized Bmal1 and Per2 expression in Aβ31-35 treated mice.
  • Interference with GLP-1R expression abolished Oxy's beneficial effects on circadian rhythm and clock genes.
  • These findings highlight the critical involvement of GLP-1R.

Conclusions:

  • Oxy effectively improves Aβ-induced circadian rhythm disorders in an AD model.
  • GLP-1R is essential for Oxy's therapeutic action, indicating it as a key target.
  • This research presents Oxy and GLP-1R as a potential novel therapeutic strategy for Alzheimer's disease.
Keywords:
Alzheimer's diseaseBmal1Per2glucagon-like peptide-1

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