PMID- 32818590
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20211204
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 737
DP  - 2020 Oct 15
TI  - Wnt-3a improves functional recovery through autophagy activation via inhibiting 
      the mTOR signaling pathway after spinal cord injury.
PG  - 135305
LID - S0304-3940(20)30575-9 [pii]
LID - 10.1016/j.neulet.2020.135305 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Gao, Kai
AU  - Gao K
AD  - 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: 
      gaohaikai88@126.com.
FAU - Niu, Jianbing
AU  - Niu J
AD  - Department of Orthopedics, Jining NO.1 People's Hospital, Jining, China. 
      Electronic address: niujianbing@126.com.
FAU - Dang, Xiaoqian
AU  - Dang X
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an Jiaotong University, Xi'an, China. Electronic address: 
      610277329@qq.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200817
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine)
RN  - 0 (Morpholines)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Triazines)
RN  - 0 (Wnt3A Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Morpholines/pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/*drug effects
MH  - Signal Transduction/*drug effects/physiology
MH  - Spinal Cord/metabolism
MH  - Spinal Cord Injuries/*drug therapy/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Triazines/pharmacology
MH  - Wnt3A Protein/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Axon regeneration
OT  - Spinal cord injury
OT  - Spinal cord neuron
OT  - Wnt-3a
OT  - mTOR signaling pathway
EDAT- 2020/08/21 06:00
MHDA- 2021/05/01 06:00
CRDT- 2020/08/21 06:00
PHST- 2020/01/16 00:00 [received]
PHST- 2020/08/11 00:00 [accepted]
PHST- 2020/08/21 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2020/08/21 06:00 [entrez]
AID - S0304-3940(20)30575-9 [pii]
AID - 10.1016/j.neulet.2020.135305 [doi]
PST - ppublish
SO  - Neurosci Lett. 2020 Oct 15;737:135305. doi: 10.1016/j.neulet.2020.135305. Epub 
      2020 Aug 17.