Exogenous BDNF Increases Mitochondrial pCREB and Alleviates Neuronal Metabolic Defects Following Mechanical Injury in a MPTP-Dependent Way

Molecular Neurobiology
Zhen XuZhang Jin

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 kn...Continue Reading

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Citations

Sep 8, 2018·ELife·Kristen R MaynardKeri Martinowich
Jul 7, 2020·International Journal of Molecular Medicine·Lingxiao ZhangTongfeng Zhao
Mar 17, 2019·Apoptosis : an International Journal on Programmed Cell Death·Hong JinBilei Wang
Jan 27, 2020·Mechanisms of Ageing and Development·Catia ScassellatiCristina Geroldi
Feb 11, 2021·Journal of Neurotrauma·Yi-Han WuVickie Shim
Jun 29, 2021·The Journal of Nutrition, Health & Aging·X Lv, H Niu

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Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

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