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Journal of Molecular Neuroscience

, Volume 67, Issue 1, pp 142–149 | Cite as

TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway

  • Yueqiang Hu
  • Wei Chen
  • Lin Wu
  • Lingfei Jiang
  • Ni Liang
  • Lulu Tan
  • Minghui Liang
  • Nong TangEmail author
Article
  • 148 Downloads

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disturbances. Dysfunction of synaptic plasticity and decline in cognitive functions are the most prominent features of AD, but the mechanisms of pathogenesis have not been well elucidated. In this paper, transforming growth factor-β1 (TGF-β1) was found to be reduced in the hippocampus of AD mouse which was accompanied by impaired pine density, synaptic plasticity, and memory function. Hippocampal injection of TGF-β1 rescued the AD-induced memory function impairment. In addition, TGF-β1 ameliorated synaptic plasticity and increased synaptic plasticity-associated protein expression including Arc, NR2B, and PSD-95 in mouse model of AD. Furthermore, we demonstrated that Akt/Wnt/β-catenin pathway protein expression in the hippocampus was suppressed in a mouse model of AD and TGF-β1 significantly enhanced the phosphorylation Akt, GSK3β, and increased the nuclear β-catenin. These results indicate that TGF-β1activates PI3K/Akt/Wnt/β-catenin signaling in mouse model of AD, which is important for promoting synaptic plasticity related to memory function. More importantly, suppression of PI3K/Akt/Wnt/β-catenin pathway compromised the beneficial effects of TGFβ1 in Alzheimer’s model. Hence, TGF-β1 shows protective effect on neurons, which might be through the PI3K/Akt/Wnt/β-catenin signaling pathway, serving as a potential target in AD pathology.

Keywords

TGF-β1 Alzheimer’s disease PI3K/Akt/Wnt/β-catenin Cognitive functions 

Notes

Funding

This work was supported by Key R & D plan of Guangxi Science and Technology Plan (No. AB16380324-02); Systematic Subject of Guangxi Key Laboratory of Basic Research of Chinese Medicine (No. 16-380-58-04); Youth Innovation Research Team of Guangxi University of Traditional Chinese Medicine (No. 2016QT004); Project Support for High Level Talent Team Development in Qi Huang Engineering of Guangxi University of Traditional Chinese Medicine (No. 2018003).

Compliance with Ethical Standards

The study protocols were approved by the relevant ethics committee of The First Affiliated Hospital of Guangxi University of Chinese Medicine, and all study procedures were performed in accordance with corresponding regulations regarding the Use of Laboratory Animals.

Conflict of Interest

The authors declare that they have no conflict of interests.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurologythe First Affiliated Hospital of Guangxi University of Chinese MedicineNanningChina
  2. 2.Key Laboratory of Guangxi Basic ChineseNanningChina
  3. 3.Scientific Laboratorial Centre Guangxi University of Chinese MedicineNanningChina
  4. 4.Graduate College of Guangxi University of Traditional Chinese MedicineNanningChina

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