Monitoring ATP dynamics in electrically active white matter tracts

  1. Andrea Trevisiol
  2. Aiman S Saab
  3. Ulrike Winkler
  4. Grit Marx
  5. Hiromi Imamura
  6. Wiebke Möbius
  7. Kathrin Kusch
  8. Klaus-Armin Nave  Is a corresponding author
  9. Johannes Hirrlinger  Is a corresponding author
  1. Max-Planck-Institute for Experimental Medicine, Germany
  2. University of Leipzig, Germany
  3. Kyoto University, Japan

Abstract

In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders.

Article and author information

Author details

  1. Andrea Trevisiol

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    Competing interests
    No competing interests declared.
  2. Aiman S Saab

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    Competing interests
    No competing interests declared.
  3. Ulrike Winkler

    Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany
    Competing interests
    No competing interests declared.
  4. Grit Marx

    Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany
    Competing interests
    No competing interests declared.
  5. Hiromi Imamura

    Graduate School of Biostudies, Kyoto University, Sakyo-ku, Japan
    Competing interests
    No competing interests declared.
  6. Wiebke Möbius

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2902-7165
  7. Kathrin Kusch

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    Competing interests
    No competing interests declared.
  8. Klaus-Armin Nave

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    For correspondence
    nave@em.mpg.de
    Competing interests
    Klaus-Armin Nave, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8724-9666
  9. Johannes Hirrlinger

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    For correspondence
    johannes.hirrlinger@medizin.uni-leipzig.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6327-0089

Funding

Deutsche Forschungsgemeinschaft

  • Johannes Hirrlinger

H2020 European Research Council

  • Klaus-Armin Nave

European Molecular Biology Organization

  • Aiman S Saab

LAVES Niedersachsen).LTLT/involved_commentsGTGTLTLTinvolved_indGTGT1LTLT/involved_indGTGTLTLT/animal_subjectsGTGTLTLThuman_subjectsGTGTLTLTinvolved_indGTGT0LTLT/involved_indGTGTLTLT/human_subjectsGTGTLTLT/xmlGTGT"

Ethics

Animal experimentation: Animals were treated in accordance with the German Protection of Animals Act (TSchG {section sign}4 Abs. 3), with the guidelines for the welfare of experimental animals issued by the European Communities Council Directive 2010/63/EU as well as the regulation of the institutional "Tierschutzkommission" and the local authorities (T04/13, T20/16; Landesdirektion Leipzig, LAVES Niedersachsen).

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: December 14, 2016
  2. Accepted: April 16, 2017
  3. Accepted Manuscript published: April 17, 2017 (version 1)
  4. Version of Record published: May 3, 2017 (version 2)

Copyright

© 2017, Trevisiol et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Andrea Trevisiol
  2. Aiman S Saab
  3. Ulrike Winkler
  4. Grit Marx
  5. Hiromi Imamura
  6. Wiebke Möbius
  7. Kathrin Kusch
  8. Klaus-Armin Nave
  9. Johannes Hirrlinger
(2017)
Monitoring ATP dynamics in electrically active white matter tracts
eLife 6:e24241.
https://doi.org/10.7554/eLife.24241
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