Affordable Access

deepdyve-link
Publisher Website

Wnt-3a improves functional recovery through autophagy activation via inhibiting the mTOR signaling pathway after spinal cord injury.

Authors
  • Gao, Kai1
  • Niu, Jianbing2
  • Dang, Xiaoqian3
  • 1 Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China; Department of Orthopedics, Jining NO.1 People's Hospital, Jining, China. Electronic address: [email protected] , (China)
  • 2 Department of Orthopedics, Jining NO.1 People's Hospital, Jining, China. Electronic address: [email protected] , (China)
  • 3 Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Neuroscience letters
Publication Date
Oct 15, 2020
Volume
737
Pages
135305–135305
Identifiers
DOI: 10.1016/j.neulet.2020.135305
PMID: 32818590
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Little is known about the effect of wnt-3a on motor nerve function and its specific molecular mechanisms after spinal cord injury (SCI). This study demonstrates that the downregulated expression levels of caspases-3, caspases-9 and chondroitin sulfate proteoglycan (CSPG) proteins and number of proportion of transferase UTP nick end labeling (TUNEL)-positive neurons by wnt-3a treatment. Then, Nissl and hematoxylin-eosin (HE) staining showed that wnt-3a significantly reduced the loss of spinal anterior horn motor neurons and promoted repair of injured spinal cord tissues after SCI. The above factors constructed a favorable microenvironment for the recovery of motor nerve function after SCI. To elucidate the molecular mechanism of neuroprotection of wnt-3a on SCI, the study showed that the expression levels of Beclin-1 and light chain (LC)3-II/I in spinal cord neurons were significantly improved by wnt-3a after SCI in vitro and vivo experiments, while the effect of wnt-3a was inhibited after mechanistic target of rapamycin (mTOR) signaling pathway being activated by MHY-1485. Besides, the level of p70S6K phosphorylation was inhibited by wnt-3a treatment, on the contrary, the level of p70S6K protein was elevated by wnt-3a, indicating that wnt-3a significantly activated neuronal autophagy by inhibiting mTOR signaling pathway after SCI. To further verify the correlation between neuroprotection of wnt-3a and autophagy, we found that after the rats and spinal cord neurons were combined treatment with wnt-3a and MHY-1485, the neuroprotection of wnt-3a on SCI was significantly inhibited. This study is the first to report that wnt-3a improves functional recovery through autophagy activation via inhibiting the mTOR signaling pathway after SCI. Copyright © 2020 Elsevier B.V. All rights reserved.

Report this publication

Statistics

Seen <100 times