PMID- 28508150
OWN - NLM
STAT- MEDLINE
DCOM- 20190204
LR  - 20201209
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 55
IP  - 4
DP  - 2018 Apr
TI  - Exogenous BDNF Increases Mitochondrial pCREB and Alleviates Neuronal Metabolic 
      Defects Following Mechanical Injury in a MPTP-Dependent Way.
PG  - 3499-3512
LID - 10.1007/s12035-017-0576-5 [doi]
AB  - Metabolic defects are common pathological phenomena following traumatic brain 
      injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic 
      factor (BDNF) is an important regulator of neuronal survival, development, 
      function, and plasticity. This study was designed to investigate the potential 
      effects of BDNF on TBI-induced metabolic defects and their underlying molecular 
      mechanisms. BDNF was added into cultured neurons to a concentration of 25, 50, 
      and 100 ng/ml, respectively, right after mechanical injury and metabolite levels 
      were analyzed 4 h post injury. The mitochondrial phosphorylated cAMP response 
      element-binding protein (pCREB) distribution and complex V synthesis, as well as 
      their roles in metabolic defects, were evaluated. We found that exogenous BDNF 
      improved metabolic defects, especially the uncoupling of oxidative 
      phosphorylation. BDNF increased pCREB in mitochondrial inner membrane and matrix 
      and promoted mitochondrial complex V synthesis. We also found that these results 
      were negatively regulated by the mitochondrial permeability transition pore 
      (MPTP) antagonist CsA and positively regulated by the MPTP agonist atractyloside. 
      BDNF's protectional effects on metabolic defects were abolished by CREB knockout. 
      When administrated in a dominant interfering CREB mutant (A-CREB) model, 
      mitochondrial pCREB accumulation could still be observed, but the synthesis of 
      complex V and alleviation of metabolic defects were repressed. Our data 
      demonstrate that exogenous BDNF mitigates neuronal metabolic defects following 
      mechanical injury by promoting the pCREB accumulation in mitochondrial inner 
      membrane and matrix, which is regulated by MPTP opening, thus facilitating the 
      synthesis of mitochondrial complex V.
FAU - Xu, Zhen
AU  - Xu Z
AD  - Department of Neurosurgery, First Affiliated Hospital of Zhejiang Chinese 
      Medicine University, 54 Youdian Lane, Hangzhou, 310006, China. 
      xuzhenhangzhou@yeah.net.
FAU - Lv, Xiao-Ai
AU  - Lv XA
AD  - Department of Surgery, First Affiliated Hospital of Zhejiang Chinese Medicine 
      University, 54 Youdian Lane, Hangzhou, 310006, China.
FAU - Dai, Qun
AU  - Dai Q
AD  - Central Laboratory, First Affiliated Hospital of Zhejiang Chinese Medicine 
      University, 54 Youdian Lane, Hangzhou, 310006, China.
FAU - Lu, Man
AU  - Lu M
AD  - Department of Anesthesiology, First Affiliated Hospital of Zhejiang Chinese 
      Medicine University, 54 Youdian Lane, Hangzhou, 310006, China.
FAU - Jin, Zhang
AU  - Jin Z
AD  - Department of Spine Surgery, The People's Hospital of Lishui, 15 Dazong Road, 
      Lishui, 323000, China.
LA  - eng
GR  - LY16H090014/Natural Science Foundation of Zhejiang Province/
GR  - 2016KYB213/zhejiang provincial medical health and science and technology project 
      foundation/
PT  - Journal Article
DEP - 20170515
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects/*metabolism
MH  - Mitochondrial Membrane Transport Proteins/*metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - Neurons/drug effects/*metabolism/*pathology
MH  - Phosphorylation/drug effects
OTO - NOTNLM
OT  - BDNF
OT  - CREB
OT  - Complex V
OT  - Metabolic defects
OT  - Mitochondria
OT  - TBI
EDAT- 2017/05/17 06:00
MHDA- 2019/02/05 06:00
CRDT- 2017/05/17 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/04/25 00:00 [accepted]
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2019/02/05 06:00 [medline]
PHST- 2017/05/17 06:00 [entrez]
AID - 10.1007/s12035-017-0576-5 [pii]
AID - 10.1007/s12035-017-0576-5 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2018 Apr;55(4):3499-3512. doi: 10.1007/s12035-017-0576-5. Epub 
      2017 May 15.