Circadian learning and memory changes in Aβ1–42 induced Alzheimer’s mice

  • Xuepei Li
  • Junwen Guan
  • Tong Sun
  • Jingguo Yang
  • Hang Yu
  • Junjie Yao
  • Zhengrong WangEmail author
Original Article


Alzheimer disease (AD) is a growing health problem globally, which causes a progressive decline in learning and memory and multiple disturbances of circadian rhythms. Six Alzheimer’s mice and six wild type (WT) mice were involved in this study. Morris Water Maze (MWM) tasks were conducted hourly to evaluate their circadian learning and memory performance. We used a single cosinor-based method to evaluate the circadian learning and memory of Alzheimer’s mice and WT mice, respectively. An area sensor was used to record locomotor activity for 2 weeks continuously, including 7 days of 12 h light/12 h dark (LD) conditions and 7 days of 12 h dark/12 h dark (DD) conditions. All WT mice showed circadian rhythm presence in learning and memory, and the peak of escape latency appeared at circadian time (CT) 12. Only one in six Alzheimer’s mice showed a circadian rhythm, but the peak of escape latency was postponed to CT20. Alzheimer’s mice showed rhythm absence under LD or DD conditions. Under LD conditions, the WT mice activity was higher than that in the Alzheimer’s mice during ZT0–5 (p = 0.007) and ZT18–23 (p = 0.353) but lower during ZT6–11 (p < 0.001) and ZT12–17 (p < 0.001). Learning and memory of wild type mice is proved to have a circadian variation throughout a day. In Alzheimer’s mice, rhythmic locomotor activity and circadian learning and memory performance were disrupted. Understanding the role of rhythmic disturbances in the process of AD may assist to identify therapeutic targets.


Alzheimer disease Circadian rhythm Learning and memory Morris water maze Locomotor activity 


Author contributions

Xuepei Li, study concept and design, animal experiments, analysis and interpretation of data,

Junwen Guan, design and interpretation data.

Tong Sun, animal experiments.

Jingguo Yang, animal experiments.

Hangyu, statistical analysis.

Junjie Yao, circadian rhythm calculation.

Zhengrong Wang, study supervision.


This study was funded by the National Nature Science Foundation of China (31371180) and the Key Technology Research and Development Program of Science and Technology of Sichuan Province (2015SZ0193).

Compliance with ethical standards

Ethics statement

This study was carried out in accordance with the recommendations of “Research Ethics Committee of College of Basic Medicine and Forensic Medicine, Sichuan University”. The protocol was approved by “College of Basic Medicine and Forensic Medicine, Sichuan University”.

Conflict of interest

No potential conflicts of interest were reported by the authors.

Statement confirming

This study did not require a registration.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic MedicineSichuan UniversityChengduPR China
  2. 2.Neurosurgery Department, West China HospitalSichuan UniversityChengduPR China
  3. 3.Institute of Neurology, Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduPR China
  4. 4.Department of Anesthesiology, Wuhan Third HostipalTongren Hospital of Wuhan UniversityWuhanPR China

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