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

被引：67

作者：

Bai, Liangjie ^{[1
]}

Mei, Xifan ^{[2
]}

Shen, Zhaoliang ^{[2
]}

Bi, Yunlong ^{[2
]}

Yuan, Yajiang ^{[2
]}

Guo, Zhanpeng ^{[2
]}

Wang, Hongyu ^{[2
]}

Zhao, Haosen ^{[2
]}

Zhou, Zipeng ^{[2
]}

Wang, Chen ^{[2
]}

Zhu, Kunming ^{[2
]}

Li, Gang ^{[2
]}

Lv, Gang ^{[1
]}

机构：

[1] China Med Univ, Affiliated Hosp 1, Dept Orthoped, Shenyang, Liaoning, Peoples R China

[2] Jinzhou Med Univ, Affiliated Hosp 1, Dept Orthoped, Jinzhou, Liaoning, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

PROTEIN-KINASE; AXON GUIDANCE; CELL-DEATH; DSCAM; IMPAIRMENT; EXPRESSION; RECEPTOR; NEUROPROTECTION; MIGRATION; APOPTOSIS;

D O I：

10.1038/srep42288

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：10

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