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Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury

Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model o...

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Autores principales: Bai, Liangjie, Mei, Xifan, Shen, Zhaoliang, Bi, Yunlong, Yuan, Yajiang, Guo, Zhanpeng, Wang, Hongyu, Zhao, Haosen, Zhou, Zipeng, Wang, Chen, Zhu, Kunming, Li, Gang, Lv, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301251/
https://www.ncbi.nlm.nih.gov/pubmed/28186165
http://dx.doi.org/10.1038/srep42288
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author Bai, Liangjie
Mei, Xifan
Shen, Zhaoliang
Bi, Yunlong
Yuan, Yajiang
Guo, Zhanpeng
Wang, Hongyu
Zhao, Haosen
Zhou, Zipeng
Wang, Chen
Zhu, Kunming
Li, Gang
Lv, Gang
author_facet Bai, Liangjie
Mei, Xifan
Shen, Zhaoliang
Bi, Yunlong
Yuan, Yajiang
Guo, Zhanpeng
Wang, Hongyu
Zhao, Haosen
Zhou, Zipeng
Wang, Chen
Zhu, Kunming
Li, Gang
Lv, Gang
author_sort Bai, Liangjie
collection PubMed
description Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K. In addition, the expression of Beclin-1 and the ratio of the light-chain 3B-II (LC3B-II)/LC3B-I in the injured spinal cord significantly increased in Netrin-1 group than those in SCI group. Moreover, the ratio of apoptotic neurons in the anterior horn of the spinal cord and the cavity area of spinal cord significantly decreased in Netrin-1 group compared with those in SCI group. In addition, Netrin-1 not only preserved motor neurons but also significantly improved motor fuction of injured rats. These results suggest that Netrin-1 improved functional recovery through autophagy stimulation by activating the AMPK/mTOR signaling pathway in rats with SCI. Thus, Netrin-1 treatment could be a novel therapeutic strategy for SCI.
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spelling pubmed-53012512017-02-15 Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury Bai, Liangjie Mei, Xifan Shen, Zhaoliang Bi, Yunlong Yuan, Yajiang Guo, Zhanpeng Wang, Hongyu Zhao, Haosen Zhou, Zipeng Wang, Chen Zhu, Kunming Li, Gang Lv, Gang Sci Rep Article Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K. In addition, the expression of Beclin-1 and the ratio of the light-chain 3B-II (LC3B-II)/LC3B-I in the injured spinal cord significantly increased in Netrin-1 group than those in SCI group. Moreover, the ratio of apoptotic neurons in the anterior horn of the spinal cord and the cavity area of spinal cord significantly decreased in Netrin-1 group compared with those in SCI group. In addition, Netrin-1 not only preserved motor neurons but also significantly improved motor fuction of injured rats. These results suggest that Netrin-1 improved functional recovery through autophagy stimulation by activating the AMPK/mTOR signaling pathway in rats with SCI. Thus, Netrin-1 treatment could be a novel therapeutic strategy for SCI. Nature Publishing Group 2017-02-10 /pmc/articles/PMC5301251/ /pubmed/28186165 http://dx.doi.org/10.1038/srep42288 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Bai, Liangjie
Mei, Xifan
Shen, Zhaoliang
Bi, Yunlong
Yuan, Yajiang
Guo, Zhanpeng
Wang, Hongyu
Zhao, Haosen
Zhou, Zipeng
Wang, Chen
Zhu, Kunming
Li, Gang
Lv, Gang
Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title_full Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title_fullStr Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title_full_unstemmed Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title_short Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
title_sort netrin-1 improves functional recovery through autophagy regulation by activating the ampk/mtor signaling pathway in rats with spinal cord injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301251/
https://www.ncbi.nlm.nih.gov/pubmed/28186165
http://dx.doi.org/10.1038/srep42288
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