Effect of acute mitochondrial dysfunction on hyperexcitable network activity in rat hippocampus in vitro

Mogens Andreasen*, Steen Nedergaard

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


Metabolic stress imposed by epileptic seizures can result in mitochondrial dysfunction, believed to act as positive feedback on epileptogenesis and seizure susceptibility. As the mechanism behind this positive feedback is unclear, the aim of the present study was to investigate the causal link between acute mitochondrial dysfunction and increased seizure susceptibility in hyperexcitable hippocampal networks. Following the induction of spontaneous interictal-like discharges, acute selective pharmacological blockade of either of the mitochondrial respiratory complexes (MRC) I-IV induced seizure-like events (SLE) in 78–100% of experiments. A similar result was obtained by uncoupling the oxidative phosphorylation (OXPHOS) but not by selective blockade of MRCV (ATP synthase) which did not induce SLE. The reactive oxygen species (ROS) scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol, 2 mM) significantly reduced the proconvulsant effect of blocking MRCI but did not reduce the proconvulsant effect of OXPHOS uncoupling. These findings indicate that acute mitochondrial dysfunction can lead to a convulsive state within a short timeframe, and that increased ROS production makes substantial contribution to such induction in addition to other mitochondrial related factors, which appears to be independent of changes in ROS and ATP production.

Original languageEnglish
Article number147193
JournalBrain Research
Number of pages8
Publication statusPublished - Jan 2021


  • Epileptic seizure
  • Hippocampus
  • Mitochondria
  • Oxidative phosphorylation
  • Oxidative stress
  • Reactive oxygen species


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