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

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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, 2017, p. 333-348.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Kislin, M, Sword, J, Fomitcheva, IV, Croom, D, Pryazhnikov, E, Lihavainen, E, Toptunov, D, Rauvala, H, Ribeiro, AS, Khiroug, L & Kirov, SA 2017, 'Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice', Journal of Neuroscience, vol. 37, no. 2, pp. 333-348. https://doi.org/10.1523/JNEUROSCI.1510-16.2016

APA

Kislin, M., Sword, J., Fomitcheva, I. V., Croom, D., Pryazhnikov, E., Lihavainen, E., ... Kirov, S. A. (2017). Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice. Journal of Neuroscience, 37(2), 333-348. https://doi.org/10.1523/JNEUROSCI.1510-16.2016

Vancouver

Author

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. / Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 2. pp. 333-348.

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@article{6d5dc2775e524e51b4db9ceab2e31f80,
title = "Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice",
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 such pathological conditions 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, while 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.SIGNIFICANCE STATEMENT: During ischemic stroke or brain trauma mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca(2+), or kill neurons by releasing pro-apoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions.",
author = "Mikhail Kislin and Jeremy Sword and Fomitcheva, {Ioulia V} and Deborah Croom and Evgeny Pryazhnikov and Eero Lihavainen and Dmytro Toptunov and Heikki Rauvala and Ribeiro, {Andre S.} and Leonard Khiroug and Kirov, {Sergei A}",
note = "Copyright {\circledC} 2016 the authors.",
year = "2017",
doi = "10.1523/JNEUROSCI.1510-16.2016",
language = "English",
volume = "37",
pages = "333--348",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "2",

}

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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

N1 - Copyright © 2016 the authors.

PY - 2017

Y1 - 2017

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 such pathological conditions 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, while 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.SIGNIFICANCE STATEMENT: During ischemic stroke or brain trauma mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca(2+), or kill neurons by releasing pro-apoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions.

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 such pathological conditions 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, while 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.SIGNIFICANCE STATEMENT: During ischemic stroke or brain trauma mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca(2+), or kill neurons by releasing pro-apoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions.

U2 - 10.1523/JNEUROSCI.1510-16.2016

DO - 10.1523/JNEUROSCI.1510-16.2016

M3 - Article

VL - 37

SP - 333

EP - 348

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 2

ER -