PMID- 28780733
OWN - NLM
STAT- MEDLINE
DCOM- 20180626
LR  - 20181113
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 42
IP  - 11
DP  - 2017 Nov
TI  - Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the 
      MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of 
      Neural Stem Cells in a Rat Model of Traumatic Brain Injury.
PG  - 3073-3083
LID - 10.1007/s11064-017-2340-7 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the 
      growth, differentiation, survival and synaptic stability of neurons. Presently, 
      the transplantation of neural stem cells (NSCs) is known to induce neural repair 
      to some extent after injury or disease. In this study, to investigate whether 
      NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further 
      enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into 
      lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, 
      western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB 
      and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after 
      transplantation. Our results showed that BDNF significantly increased the 
      expression levels of the TrkB receptor gene and the phosphorylation of the TrkB 
      protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and 
      postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted 
      groups compared with those in the NSCs-transplanted groups throughout the 
      experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 
      2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the 
      treatment of injury or cell death, was upregulated by BDNF overexpression. 
      Therefore, we determined that the increased synaptic proteins level implicated in 
      synaptogenesis might be associated with the activation of the MAPK/Erk1/2 
      signaling pathway and the upregulation of the antioxidant agent Trx modified by 
      BDNF-TrkB following the BDNF/NSCs transplantation after TBI.
FAU - Chen, Tao
AU  - Chen T
AD  - Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, 116011, China.
FAU - Wu, Yu
AU  - Wu Y
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China.
FAU - Wang, Yuzi
AU  - Wang Y
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China.
FAU - Zhu, Jigao
AU  - Zhu J
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China.
FAU - Chu, Haiying
AU  - Chu H
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China.
FAU - Kong, Li
AU  - Kong L
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China.
FAU - Yin, Liangwei
AU  - Yin L
AD  - Department of Oncology, Dalian Central Hospital, Dalian, 116033, Liaoning, China. 
      lwyin2008@163.com.
FAU - Ma, Haiying
AU  - Ma H
AD  - Department of Histology and Embryology, Dalian Medical University, Dalian, 
      116044, China. hyma20060602@aliyun.com.
LA  - eng
PT  - Journal Article
DEP - 20170805
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Txn1 protein, rat)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Brain Injuries, Traumatic/*metabolism/therapy
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*biosynthesis
MH  - Disease Models, Animal
MH  - Embryonic Stem Cells/transplantation
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinase Kinases/*biosynthesis/metabolism
MH  - NF-E2-Related Factor 2/*biosynthesis/metabolism
MH  - Neural Stem Cells/*transplantation
MH  - Rats
MH  - Rats, Wistar
MH  - Stem Cell Transplantation/methods
MH  - Synapses/drug effects/metabolism
MH  - Thioredoxins/*biosynthesis/metabolism
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Differentiation
OT  - MAPK/Erk
OT  - PSD-95
OT  - Synaptogenesis
OT  - Thioredoxin
OT  - Transplantation
OT  - Traumatic brain injury
OT  - TrkB
EDAT- 2017/08/07 06:00
MHDA- 2018/06/27 06:00
CRDT- 2017/08/07 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/06/20 00:00 [accepted]
PHST- 2017/06/05 00:00 [revised]
PHST- 2017/08/07 06:00 [pubmed]
PHST- 2018/06/27 06:00 [medline]
PHST- 2017/08/07 06:00 [entrez]
AID - 10.1007/s11064-017-2340-7 [pii]
AID - 10.1007/s11064-017-2340-7 [doi]
PST - ppublish
SO  - Neurochem Res. 2017 Nov;42(11):3073-3083. doi: 10.1007/s11064-017-2340-7. Epub 
      2017 Aug 5.