Mitochondria within axons and glial cells are important for healthy axonal function. Mitochondria have a multitude of functions and features, two of which are ATP production and the production of reactive oxygen species (ROS). By using viral probes and multiphoton microscopy, we are able to observe and quantify several parameters (ATP, ROS, Calcium, pH, morphology) of mitochondrial physiology in vivo in both axons and glial cells. We used different paradigms to analyze the role of mitochondria and metabolism in the maintenance of myelin sheath and myelinated axons and in peripheral nerve diseases.

fig6.1 suite1

We implemented two-photons microscopy and CARS imaging in our lab. The use of Coherent Anti-Stokes Raman Scattering (CARS) imaging allows us to image myelin real-time in vivo without labelling.

Astrocytes and oligodendrocytes, cells termed glia within the central nervous system (CNS) are hypothesized to supply lactate to the axon which can be converted into pyruvate to maintain substrates for the electron transport chain in order to produce cellular energy in the form of ATP. Lactate is readily produced as the terminal product of glycolysis, an inefficient but common pathway to produce ATP within glia in the CNS. Lactate is hypothesized to be transported down its gradient from glia to neurons through monocarboxylate transporters, different isoforms of which are expressed on glia and neurons. How important lactate is to a healthy or damaged axon is not understood. Using state of the art live imaging approaches, the aim of this project is to understand the role of glial derived lactate has to play in myelinated and demyelinated axons, particularly in the production of ATP and axonal degeneration, an important and yet poorly understood pathological feature of multiple sclerosis.

Our approaches rely on:

  • In vivo imaging
  • Animal models
  • Viral transductions
  • Cre/Lox system
  • Histology
  • CARS imaging
  • Electrophysiology

Major publications

Hajjar H et al., J Biophotonics. doi: 10.1002/jbio.201800186, 2018

Tricaud N, Front Cell Neurosci. 5;11:414, 2018.

Fernando RN et al., Nat Commun. 20;7:12186, 2016.

Gonzalez S et al., Mitochondrion. 23:32-41, 2015.

Gonzalez S. et al., Nature Protocols. 9(5):1160-9, 2014

Bartolami S et al., Med Sci. 28(4):341-3, 2012

Jacob C et al., Nat. Neurosci. 14:429-436, 2011

Cotter L et al., Science. 268:1415-18, 2010

Özçelik M et al., J. Neurosci. 30(11): 4120-31, 2010

Collaborations

  • Roman Chrast, Karolinska Institute, Sweden
  • Fatiha Nothias, UPMC, Paris, France
  • Florence Perrin, MMDN, Montpellier
  • Hwan Tae Park, Dong-A University, Busan, South Korea
  • Hervé Rigneault, Institut Fresnel, Marseille, France
  • Guy Lenaers  PREMMi, Angers, France

Financements

logo Inserm    AFM    ARSEP    FRM    LOGO ERC    

logo epigenmed     logo erare     MarieCurie      logo regionLR

Contact

Tricaud Nicolas