title: Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury.
abstract: 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.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Yajiang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Haosen
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Kunming
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lv
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000075388:Netrin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000263:Adenylate Kinase; D000071186:Beclin-1; D053148:Caspase 3; D008869:Microtubule-Associated Proteins; D000075388:Netrin-1; D058570:TOR Serine-Threonine Kinases; C526109:Anxa3 protein, rat