Synaptic Mitochondria are More Susceptible to Traumatic Brain Injury-induced Oxidative Damage and Respiratory Dysfunction than Non-synaptic Mitochondria

Rachel L. Hill, Jacqueline R. Kulbe, Indrapal N. Singh, Juan A. Wang, Edward D. Hall

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP. Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic populations. Synaptic mitochondria are reported to be more vulnerable to injury; however, this is the first study to characterize the temporal profile of synaptic and non-synaptic mitochondria following TBI, including investigation of respiratory dysfunction and oxidative damage to mitochondrial proteins between 3 and 120 h following injury. These results indicate that synaptic mitochondria are indeed the more vulnerable population, showing both more rapid and severe impairments than non-synaptic mitochondria. By 24 h, synaptic respiration is significantly impaired compared to synaptic sham, whereas non-synaptic respiration does not decline significantly until 48 h. Decreases in respiration are associated with increases in oxidative damage to synaptic and non-synaptic mitochondrial proteins at 48 h and 72 h, respectively. These results indicate that the therapeutic window for mitochondria-targeted pharmacological neuroprotectants to prevent respiratory dysfunction is shorter for the more vulnerable synaptic mitochondria than for the non-synaptic population.

Original languageEnglish
Pages (from-to)265-283
Number of pages19
JournalNeuroscience
Volume386
DOIs
StatePublished - Aug 21 2018

Bibliographical note

Publisher Copyright:
© 2018 IBRO

Keywords

  • lipid peroxidation
  • non-synaptic mitochondria
  • oxidative damage
  • synaptic mitochondria
  • traumatic brain injury

ASJC Scopus subject areas

  • General Neuroscience

Fingerprint

Dive into the research topics of 'Synaptic Mitochondria are More Susceptible to Traumatic Brain Injury-induced Oxidative Damage and Respiratory Dysfunction than Non-synaptic Mitochondria'. Together they form a unique fingerprint.

Cite this