Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice

Mikhail Kislin, Jeremy Sword, Ioulia V. Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S. Ribeiro, Leonard Khiroug, Sergei A. Kirov

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1-2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries.

Original languageEnglish (US)
Pages (from-to)333-348
Number of pages16
JournalJournal of Neuroscience
Volume37
Issue number2
DOIs
StatePublished - Jan 11 2017

Keywords

  • Brain trauma
  • Dendrite
  • Mitochondria
  • Stroke
  • Structural dynamics
  • Two-photon in vivo imaging

ASJC Scopus subject areas

  • Neuroscience(all)

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