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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Bibliographic Details
Published in:eLife 2017-04, Vol.6
Main Authors: Trevisiol, Andrea, Saab, Aiman S, Winkler, Ulrike, Marx, Grit, Imamura, Hiromi, Möbius, Wiebke, Kusch, Kathrin, Nave, Klaus-Armin, Hirrlinger, Johannes
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analysis
Animal models
Animals
ATP
ATP (Adenosine triphosphate)
axon
Axons
Electroencephalography
Energy
Energy metabolism
Fluorescence Resonance Energy Transfer
Genes, Reporter
Glucose
Glucose metabolism
Glycolysis
Health aspects
Homeostasis
imaging
Lactic acid
Metabolism
Mice
Mice, Transgenic
Microscopy
Microscopy, Confocal
Mitochondria
Myelin
Nervous system
Neurodegeneration
Neurodegenerative diseases
Neuronal-glial interactions
Neuroscience
Optic nerve
Optic Nerve - chemistry
Optic Nerve - physiology
Optical Imaging
Physiological aspects
Physiology
Rodents
Sensors
Substantia alba
White Matter - chemistry
White Matter - physiology
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.24241