Monitoring ATP dynamics in electrically active white matter tracts
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 exp...
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doaj-5086699597c04e8a86a1cc312f1942f12021-05-05T13:24:47ZengeLife Sciences Publications LtdeLife2050-084X2017-04-01610.7554/eLife.24241Monitoring ATP dynamics in electrically active white matter tractsAndrea Trevisiol0Aiman S Saab1Ulrike Winkler2Grit Marx3Hiromi Imamura4Wiebke Möbius5https://orcid.org/0000-0002-2902-7165Kathrin Kusch6Klaus-Armin Nave7https://orcid.org/0000-0001-8724-9666Johannes Hirrlinger8https://orcid.org/0000-0002-6327-0089Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, GermanyDepartment of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, SwitzerlandCarl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, GermanyCarl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, GermanyGraduate School of Biostudies, Kyoto University, Kyoto, JapanDepartment of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, GermanyDepartment of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, GermanyDepartment of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, GermanyDepartment of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, GermanyIn 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.https://elifesciences.org/articles/24241ATPaxonmyelinimaging |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Trevisiol Aiman S Saab Ulrike Winkler Grit Marx Hiromi Imamura Wiebke Möbius Kathrin Kusch Klaus-Armin Nave Johannes Hirrlinger |
spellingShingle |
Andrea Trevisiol Aiman S Saab Ulrike Winkler Grit Marx Hiromi Imamura Wiebke Möbius Kathrin Kusch Klaus-Armin Nave Johannes Hirrlinger Monitoring ATP dynamics in electrically active white matter tracts eLife ATP axon myelin imaging |
author_facet |
Andrea Trevisiol Aiman S Saab Ulrike Winkler Grit Marx Hiromi Imamura Wiebke Möbius Kathrin Kusch Klaus-Armin Nave Johannes Hirrlinger |
author_sort |
Andrea Trevisiol |
title |
Monitoring ATP dynamics in electrically active white matter tracts |
title_short |
Monitoring ATP dynamics in electrically active white matter tracts |
title_full |
Monitoring ATP dynamics in electrically active white matter tracts |
title_fullStr |
Monitoring ATP dynamics in electrically active white matter tracts |
title_full_unstemmed |
Monitoring ATP dynamics in electrically active white matter tracts |
title_sort |
monitoring atp dynamics in electrically active white matter tracts |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-04-01 |
description |
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. |
topic |
ATP axon myelin imaging |
url |
https://elifesciences.org/articles/24241 |
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