Abstract:
: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.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Xu Z,Lv XA,Dai Q,Lu M,Jin Zdoi
10.1007/s12035-017-0576-5subject
Has Abstractpub_date
2018-04-01 00:00:00pages
3499-3512issue
4eissn
0893-7648issn
1559-1182pii
10.1007/s12035-017-0576-5journal_volume
55pub_type
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