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Neurochemical Research

, Volume 42, Issue 8, pp 2326–2335 | Cite as

Liraglutide Improves Water Maze Learning and Memory Performance While Reduces Hyperphosphorylation of Tau and Neurofilaments in APP/PS1/Tau Triple Transgenic Mice

  • Shuyi Chen
  • Jie Sun
  • Gang Zhao
  • Ai Guo
  • Yanlin Chen
  • Rongxia Fu
  • Yanqiu DengEmail author
Original Paper

Abstract

The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 μg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes. The Morris water maze (MWM) was used to assess the spatial learning and memory. Liraglutide decreased levels of hyperphosphorylated tau and NFs in 3 × Tg liraglutide-treated (Tg + LIR) mice, increased ERK phosphorylation, and decreased JNK phosphorylation. Liraglutide also decreased the number of degenerative neurons in the hippocampus and cortex of Tg + LIR mice, and shortened their escape latencies and increased their hidden platform crossings in the MWM task. Liraglutide did not significantly affect the animals’ body weight (BW) or fasting blood glucose. Liraglutide can reduce hyperphosphorylation of tau and NFs and reduce neuronal degeneration, apparently through alterations in JNK and ERK signaling, which may be related to its positive effects on AD-like learning and memory impairment.

Keywords

Alzheimer disease Liraglutide 3 × Tg mice Tau ERK JNK 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81270422, 30973156) and the National Training Programs of Innovation and Entrepreneurship for Undergraduates (201610062013).

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Shuyi Chen
    • 1
  • Jie Sun
    • 1
  • Gang Zhao
    • 2
  • Ai Guo
    • 1
  • Yanlin Chen
    • 1
  • Rongxia Fu
    • 3
  • Yanqiu Deng
    • 1
    • 4
    Email author
  1. 1.Pathophysiology Department, School of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  2. 2.Department of Pathology, Tianjin Cancer HospitalTianjin Medical UniversityTianjinChina
  3. 3.Food science and Biological Engineering DepartmentTianjin Agriculture UniversityTianjinChina
  4. 4.TianjinChina

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