Monitoring ATP dynamics in electrically active white matter tracts
- Max-Planck-Institute for Experimental Medicine, Germany
- University of Leipzig, Germany
- 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
Johannes Hirrlinger
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).
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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Monitoring ATP dynamics in electrically active white matter tracts
eLife 6:e24241.
https://doi.org/10.7554/eLife.24241
