PMID- 30139740
OWN - NLM
STAT- MEDLINE
DCOM- 20190304
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 40
DP  - 2018 Oct 5
TI  - Neuron activity-induced Wnt signaling up-regulates expression of brain-derived 
      neurotrophic factor in the pain neural circuit.
PG  - 15641-15651
LID - 10.1074/jbc.RA118.002840 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a master regulator of synaptic 
      plasticity in various neural circuits of the mammalian central nervous system. 
      Neuron activity-induced BDNF gene expression is regulated through the Ca(2+)/CREB 
      pathway, but other regulatory factors may also be involved in controlling BDNF 
      levels. We report here that Wnt/beta-catenin signaling plays a key role in 
      controlling neuron activity-regulated BDNF expression. Using primary cortical 
      cultures, we show that blockade of Wnt/beta-catenin signaling inhibits the BDNF 
      up-regulation that is induced by activation of the N-methyl-d-aspartic acid 
      (NMDA) receptor and that activation of the Wnt/beta-catenin signaling pathway 
      stimulates BDNF expression. In vivo, Wnt/beta-catenin signaling activated BDNF 
      expression and was required for peripheral pain-induced up-regulation of BDNF in 
      the mouse spine. We also found that conditional deletion of one copy of either 
      Wntless (Wls) or beta-catenin by Nestin-Cre-mediated recombination is sufficient to 
      inhibit the pain-induced up-regulation of BDNF. We further show that the 
      Wnt/beta-catenin/BDNF axis in the spinal neural circuit plays an important role in 
      regulating capsaicin-induced pain. These results indicate that neuron 
      activity-induced Wnt signaling stimulates BDNF expression in the pain neural 
      circuits. We propose that pain-induced Wnt secretion may provide an additional 
      mechanism for intercellular coordination of BDNF expression in the neural 
      circuit.
CI  - (c) 2018 Zhang et al.
FAU - Zhang, Wenping
AU  - Zhang W
AD  - From the Departments of Neuroscience and Cell Biology and.
AD  - the College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, 
      China.
FAU - Shi, Yuqiang
AU  - Shi Y
AD  - From the Departments of Neuroscience and Cell Biology and.
FAU - Peng, Yanxi
AU  - Peng Y
AD  - the School of Pharmaceutical Sciences and Laboratory Animal Center of Sun Yat-Sen 
      University, Guangzhou 510275, China.
AD  - the Basic Medical Department, Xiangnan University, Chenzhou 423000, China, and.
FAU - Zhong, Ling
AU  - Zhong L
AD  - the School of Pharmaceutical Sciences and Laboratory Animal Center of Sun Yat-Sen 
      University, Guangzhou 510275, China.
AD  - the Shenzhen Center for ADR Monitoring, Shenzhen 518001, China.
FAU - Zhu, Shuang
AU  - Zhu S
AD  - Ophthalmology, University of Texas Medical Branch, Galveston, Texas 77555.
FAU - Zhang, Wenbo
AU  - Zhang W
AD  - From the Departments of Neuroscience and Cell Biology and.
AD  - Ophthalmology, University of Texas Medical Branch, Galveston, Texas 77555.
FAU - Tang, Shao-Jun
AU  - Tang SJ
AUID- ORCID: 0000-0002-6076-5481
AD  - From the Departments of Neuroscience and Cell Biology and shtang@utmb.edu.
LA  - eng
GR  - R01 DA036165/DA/NIDA NIH HHS/United States
GR  - R01 EY026629/EY/NEI NIH HHS/United States
GR  - R01 NS079166/NS/NINDS NIH HHS/United States
GR  - R01 NS095747/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180823
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ANA 12 compound)
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Azepines)
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Gpr177 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Wnt3A Protein)
RN  - 0 (Wnt3a protein, mouse)
RN  - 0 (beta Catenin)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/pharmacology
MH  - Azepines/pharmacology
MH  - Benzamides/pharmacology
MH  - Brain-Derived Neurotrophic Factor/agonists/*genetics/metabolism
MH  - Capsaicin/administration & dosage
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation
MH  - Hindlimb
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Plasticity/physiology
MH  - Neurons/drug effects/*metabolism
MH  - Pain/chemically induced/drug therapy/*genetics/physiopathology
MH  - Primary Cell Culture
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/genetics/metabolism
MH  - Spinal Cord/drug effects/metabolism/physiopathology
MH  - Transcription, Genetic
MH  - Wnt Signaling Pathway
MH  - Wnt3A Protein/*genetics/metabolism
MH  - beta Catenin/*genetics/metabolism
PMC - PMC6177598
OTO - NOTNLM
OT  - Wnt signaling
OT  - beta-catenin (B-catenin)
OT  - brain-derived neurotrophic factor (BDNF)
OT  - gene expression
OT  - neuron
OT  - pain
OT  - synapse
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2018/08/25 06:00
MHDA- 2019/03/05 06:00
PMCR- 2019/10/05
CRDT- 2018/08/25 06:00
PHST- 2018/03/10 00:00 [received]
PHST- 2018/05/11 00:00 [revised]
PHST- 2018/08/25 06:00 [pubmed]
PHST- 2019/03/05 06:00 [medline]
PHST- 2018/08/25 06:00 [entrez]
PHST- 2019/10/05 00:00 [pmc-release]
AID - S0021-9258(20)35265-0 [pii]
AID - RA118.002840 [pii]
AID - 10.1074/jbc.RA118.002840 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Oct 5;293(40):15641-15651. doi: 10.1074/jbc.RA118.002840. Epub 
      2018 Aug 23.