Neurochemical Research

, Volume 42, Issue 8, pp 2336–2343 | Cite as

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury

  • Zhaoliang Shen
  • Zipeng Zhou
  • Shuang Gao
  • Yue Guo
  • Kai Gao
  • Haoyu Wang
  • Xiaoqian Dang
Original Paper


The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.


Melatonin Wnt/β-catenin Spinal cord injury Apoptosis 



Spinal cord injury


Low-density lipoprotein receptor related protein 6 phosphorylation


Lymphoid enhancer factor-1


Central nervous system




Nuclear factor erythroid 2-related factor 2


Hypoxia-inducible factor


Nuclear factor kappa B


Superoxide dismutase








Dulbecco’s modified Eagle’s medium


Fetal bovine serum


Small interference RNA


Basso, Beattie, and Bresnahan scores


Transferase-mediated deoxyuridine triphosphate nick end labeling


One-way analysis of variance


Standard error of the mean



This work was supported by the National Natural Science Foundation of China (NSFC) (Grant Nos. 81471854, 81671907 and 81601727). The authors thank the other researchers for their valuable technical assistance in this work.

Compliance with Ethical Standards

Conflict of interest

The authors that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Zhaoliang Shen
    • 1
    • 2
    • 3
  • Zipeng Zhou
    • 3
  • Shuang Gao
    • 4
  • Yue Guo
    • 3
  • Kai Gao
    • 5
  • Haoyu Wang
    • 1
  • Xiaoqian Dang
    • 1
  1. 1.Department of OrthopedicsThe Second Affiliated Hospital of Xi’an Jiaotong University (Xibei Hospital)Xi’anChina
  2. 2.Department of OrthopedicsSecond Hospital of JinzhouJinzhouChina
  3. 3.Department of OrthopedicsFirst Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
  4. 4.Jinzhou Medical UniversityJinzhouChina
  5. 5.Department of OrthopedicsJining NO.1 People’s HospitalJiningChina

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