Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury.
Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury.
复制标题
Netrin-1 通过激活脊髓损伤大鼠的 AMPK/mTOR 信号通路，通过自噬调节改善功能恢复。
DOI：
10.1038/srep42288
复制
发表时间：
2017-02-10
影响因子：
4.6
通讯作者：
Lv G
中科院分区：
文献类型：
--
作者：
Bai L;Mei X;Shen Z;Bi Y;Yuan Y;Guo Z;Wang H;Zhao H;Zhou Z;Wang C;Zhu K;Li G;Lv G
自噬是降解细胞质聚集蛋白和受损细胞器的过程，在脊髓损伤的发生发展中起着重要作用。在这项研究中，我们研究了Netrin-1的治疗作用及其对SCI后自噬调节的潜在机制。建立大鼠SCI模型并用于分析。结果显示，Netrin-1的施用不仅显著增强AMP活化蛋白激酶（AMPK）的磷酸化，而且降低了哺乳动物雷帕霉素靶蛋白（mTOR）和P70S6K的磷酸化。Netrin-1组Beclin-1的表达及轻链3B-II（LC3B-II）/LC3B-I的比值较SCI组明显升高。Netrin-1组脊髓前角和脊髓空洞区神经元凋亡率较SCI组明显降低。此外，Netrin-1不仅保留了运动神经元，还显着改善了损伤大鼠的运动功能。这些结果表明，Netrin-1通过激活SCI大鼠的AMPK/mTOR信号通路，通过自噬刺激改善功能恢复。因此，Netrin-1治疗可能是SCI的一种新的治疗策略。
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.