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 language | English (US) |
|---|---|
| Pages (from-to) | 333-348 |
| Number of pages | 16 |
| Journal | Journal of Neuroscience |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 11 2017 |
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Keywords
- Brain trauma
- Dendrite
- Mitochondria
- Stroke
- Structural dynamics
- Two-photon in vivo imaging
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice. / Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.; Khiroug, Leonard; Kirov, Sergei A.
In: Journal of Neuroscience, Vol. 37, No. 2, 11.01.2017, p. 333-348.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice
AU - Kislin, Mikhail
AU - Sword, Jeremy
AU - Fomitcheva, Ioulia V.
AU - Croom, Deborah
AU - Pryazhnikov, Evgeny
AU - Lihavainen, Eero
AU - Toptunov, Dmytro
AU - Rauvala, Heikki
AU - Ribeiro, Andre S.
AU - Khiroug, Leonard
AU - Kirov, Sergei A.
PY - 2017/1/11
Y1 - 2017/1/11
N2 - 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.
AB - 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.
KW - Brain trauma
KW - Dendrite
KW - Mitochondria
KW - Stroke
KW - Structural dynamics
KW - Two-photon in vivo imaging
UR - http://www.scopus.com/inward/record.url?scp=85009727141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85009727141&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1510-16.2016
DO - 10.1523/JNEUROSCI.1510-16.2016
M3 - Article
C2 - 28077713
AN - SCOPUS:85009727141
VL - 37
SP - 333
EP - 348
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 2
ER -