In vivo time-lapse imaging of mitochondria in healthy and diseased peripheral myelin sheath

González, Sergio; Fernando, Ruani; Berthelot, Jade; Perrin-Tricaud, Claire; Sarzi, Emmanuelle; Chrast, Roman; Lenaers, Guy; Tricaud, Nicolas

doi:10.1016/j.mito.2015.05.004

Cited by 19 publications

(27 citation statements)

References 46 publications

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“…We did not observe any significant change in the frequency of each size category ( Fig. 2B), suggesting mitochondria slowed down after the trigger of demyelination without fragmenting as seen previously after animal death (16). Mito-Sypher reported a significant and persistent increase in pH starting 120 minutes after the injury (Fig.…”

Section: Sciatic Nerve Injury Induces Mitochondrial Calcium Release Isupporting

confidence: 75%

“…The right sciatic nerves of 2 months old mice were injected with a solution of adenovirus or AAV expressing different fluorescent probes that infected myelinating Schwann cells in vivo (16)(17)(18). Three weeks later, mice were anesthetized, their sciatic nerve exposed and placed under a multiphoton microscope allowing mSC mitochondria time-lapse imaging in physiological conditions ( Fig.…”

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

“…Three weeks later, mice were anesthetized, their sciatic nerve exposed and placed under a multiphoton microscope allowing mSC mitochondria time-lapse imaging in physiological conditions ( Fig. 1A) (16). We used mito-Dsred2 (16) to measure mitochondrial size and movements, mito-Sypher (19) for mitochondrial matrix pH, mito-GCaMP2 (20) for mitochondrial matrix calcium content and the same probe without the peptide targeting to mitochondria to assess of cytoplasmic calcium content (cyto-GCaMP2).…”

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

“…We used mito-Dsred2 (16) to measure mitochondrial size and movements, mito-Sypher (19) for mitochondrial matrix pH, mito-GCaMP2 (20) for mitochondrial matrix calcium content and the same probe without the peptide targeting to mitochondria to assess of cytoplasmic calcium content (cyto-GCaMP2). Mito-Dsred2 probe was previously validated in vivo (16). Mito-GCaMP2 and cyto-GCaMP2 were validated by incubating infected nerve in successive baths of calcium chelator EDTA and calcium donor CaCl2 in a mild saponin detergent ( Fig.…”

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

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Schwann cell demyelination is triggered by a transient mitochondrial calcium release through Voltage Dependent Anion Channel 1

Tricaud

Gautier

Hameren

et al. 2019

Preprint

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The maintenance of the myelin sheath by Schwann cells around peripheral nerve axons is essential for the rapid propagation of action potentials. A large number of peripheral neuropathies results for the loss of this myelin sheath, a process called demyelination. Demyelination is a program of cell dedifferentiation characterized by reprograming and several catabolic and anabolic events. This process was best characterized in Wallerian demyelination that occurs following nerve injury. In this model, the earliest well characterized steps are MAPK pathways activation and cJun phosphorylation and nuclear localization starting around 4hrs after nerve injury. Here we show, using in vivo imaging of virally-delivered fluorescent probes to mitochondria, that Schwann cell mitochondria pH, motility and calcium are altered as soon as 1hr after nerve injury. Mitochondrial calcium release through VDAC1 mitochondrial channel and mPTP directly induced Schwann cell demyelination via MAPK and c-Jun activation. Decreasing mitochondrial calcium release through VDAC1 silencing or TRO19622 blocking prevented MAPK and cJun activation and demyelination. VDAC1 opening with Methyl Jasmonate induced these cellular mechanisms in absence of nerve injury. Taken together, these data indicate that mitochondria calcium homeostasis through VDAC1 is instrumental in the Schwann cell demyelination process and therefore provide a molecular basis for an anti-demyelinating drug approach.

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Section: Sciatic Nerve Injury Induces Mitochondrial Calcium Release Isupporting

confidence: 75%

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

Section: Live Imaging Of Msc Mitochondria and Fluorescent Probes Valimentioning

confidence: 99%

See 2 more Smart Citations

Schwann cell demyelination is triggered by a transient mitochondrial calcium release through Voltage Dependent Anion Channel 1

Tricaud

Gautier

Hameren

et al. 2019

Preprint

Self Cite

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show abstract

“…We first anesthetized adult mice and, after a small surgery, gently placed their sciatic nerve under the lens of the multiphoton microscope as previously described . Nerve of control mice were not illuminated while experimental mouse nerves were illuminated for THG or CARS imaging (1 minute at different laser power).…”

Section: Resultsmentioning

confidence: 99%

Label‐free non‐linear microscopy to measure myelin outcome in a rodent model of Charcot‐Marie‐Tooth diseases

Hajjar

Boukhaddaoui

Rizgui

et al. 2018

Journal of Biophotonics

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Myelin sheath produced by Schwann cells covers and nurtures axons to speed up nerve conduction in peripheral nerves. Demyelinating peripheral neuropathies result from the loss of this myelin sheath and so far, no treatment exists to prevent Schwann cell demyelination. One major hurdle to design a therapy for demyelination is the lack of reliable measures to evaluate the outcome of the treatment on peripheral myelin in patients but also in living animal models. Non-linear microscopy techniques which include second harmonic generation (SHG), third harmonic generation (THG) and coherent anti-stokes Raman scattering (CARS) were used to image myelin ex vivo and in vivo in the sciatic nerve of healthy and demyelinating mice and rats. SHG did not label myelin and THG required too much light power to be compatible with live imaging. CARS is the most reliable of these techniques for in vivo imaging and it allows for the analysis and quantification of myelin defects in a rat model of CMT1A disease. This microscopic technique therefore constitutes a promising, reliable and robust readout tool in the development of new treatments for demyelinating peripheral neuropathies.

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Wallerian demyelination: chronicle of a cellular cataclysm

Tricaud

Park

2017

Cell. Mol. Life Sci.

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Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, a process termed demyelination. In this review, we chronologically describe this program starting from the late and visible features of myelin destruction and going backward to the initial molecular steps that trigger the nuclear reprogramming few hours after injury. Wallerian demyelination is a wonderful model for myelin degeneration occurring in the diverse forms of demyelinating peripheral neuropathies that plague human beings.

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In vivo time-lapse imaging of mitochondria in healthy and diseased peripheral myelin sheath

Cited by 19 publications

References 46 publications

Schwann cell demyelination is triggered by a transient mitochondrial calcium release through Voltage Dependent Anion Channel 1

Schwann cell demyelination is triggered by a transient mitochondrial calcium release through Voltage Dependent Anion Channel 1

Label‐free non‐linear microscopy to measure myelin outcome in a rodent model of Charcot‐Marie‐Tooth diseases

Wallerian demyelination: chronicle of a cellular cataclysm

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