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Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats

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Abstract

Autophagy occurs prior to apoptosis and plays an important role in cell death regulation during spinal cord injury (SCI). This study aimed to determine the effects and potential mechanism of the glucagon-like peptide-1 (GLP-1) agonist extendin-4 (Ex-4) in SCI. Seventy-two male Sprague Dawley rats were randomly assigned to sham, SCI, 2.5 μg Ex-4, and 10 μg Ex-4 groups. To induce SCI, a 10-g iron rod was dropped from a 20-mm height to the spinal cord surface. Ex-4 was administered via intraperitoneal injection immediately after surgery. Motor function evaluation with the Basso Beattie Bresnahan (BBB) locomotor rating scale indicated significantly increased scores (p < 0.01) in the Ex-4-treated groups, especially 10 μg, which demonstrated the neuroprotective effect of Ex-4 after SCI. The light chain 3-II (LC3-II) and Beclin 1 protein expression determined via western blot and the number of autophagy-positive neurons via immunofluorescence double labeling were increased by Ex-4, which supports promotion of autophagy (p < 0.01). The caspase-3 protein level and neuronal apoptosis via transferase UTP nick end labeling (TUNEL)/NeuN/DAPI double labeling were significantly reduced in the Ex-4-treated groups, which indicates anti-apoptotic effects (p < 0.01). Finally, histological assessment via Nissl staining demonstrated the Ex-4 groups exhibited a significantly greater number of surviving neurons and less cavity (p < 0.01). To our knowledge, this is the first study to indicate that Ex-4 significantly enhances motor function in rats after SCI, and these effects are associated with the promotion of autophagy and inhibition of apoptosis.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (Grant No. 81272074); the Program for Liaoning Excellent Talents in University (Grant No. 2014091); and the Aohongboze Graduate Sci-tech Innovation Foundation, the President Fund of Liaoning Medical University (Grant No. AH2014012).

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China

    Hao-Tian Li, Xing-Zhang Zhao, Gang Li, Zhi-Qiang Jia, Ping Sun, Ji-Quan Wang, Zhong-Kai Fan & Gang Lv

  2. Postgraduate Training Base of General Hospital of Armed Police Forces, Liaoning Medical University, Beijing, 100039, China

    Xin-Ran Zhang

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  1. Hao-Tian Li
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  2. Xing-Zhang Zhao
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  3. Xin-Ran Zhang
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  4. Gang Li
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  5. Zhi-Qiang Jia
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  7. Ji-Quan Wang
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  8. Zhong-Kai Fan
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  9. Gang Lv
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Correspondence to Zhong-Kai Fan or Gang Lv.

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Li, HT., Zhao, XZ., Zhang, XR. et al. Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats. Mol Neurobiol 53, 4073–4082 (2016). https://doi.org/10.1007/s12035-015-9327-7

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  • DOI: https://doi.org/10.1007/s12035-015-9327-7

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