Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia.
In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore...
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2020-11-01
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Online Access: | https://doi.org/10.1371/journal.pbio.3000943 |
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doaj-61c88fbc528c462a986b38a93992e1172021-07-02T21:22:09ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852020-11-011811e300094310.1371/journal.pbio.3000943Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia.Andrea TrevisiolKathrin KuschAnna M SteyerIngo GregorChristos NardisUlrike WinklerSusanne KöhlerAlejandro RestrepoWiebke MöbiusHauke B WernerKlaus-Armin NaveJohannes HirrlingerIn several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon-myelin unit contribute to the phenotype of Plpnull/y mice.https://doi.org/10.1371/journal.pbio.3000943 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Trevisiol Kathrin Kusch Anna M Steyer Ingo Gregor Christos Nardis Ulrike Winkler Susanne Köhler Alejandro Restrepo Wiebke Möbius Hauke B Werner Klaus-Armin Nave Johannes Hirrlinger |
spellingShingle |
Andrea Trevisiol Kathrin Kusch Anna M Steyer Ingo Gregor Christos Nardis Ulrike Winkler Susanne Köhler Alejandro Restrepo Wiebke Möbius Hauke B Werner Klaus-Armin Nave Johannes Hirrlinger Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. PLoS Biology |
author_facet |
Andrea Trevisiol Kathrin Kusch Anna M Steyer Ingo Gregor Christos Nardis Ulrike Winkler Susanne Köhler Alejandro Restrepo Wiebke Möbius Hauke B Werner Klaus-Armin Nave Johannes Hirrlinger |
author_sort |
Andrea Trevisiol |
title |
Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
title_short |
Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
title_full |
Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
title_fullStr |
Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
title_full_unstemmed |
Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
title_sort |
structural myelin defects are associated with low axonal atp levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2020-11-01 |
description |
In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon-myelin unit contribute to the phenotype of Plpnull/y mice. |
url |
https://doi.org/10.1371/journal.pbio.3000943 |
work_keys_str_mv |
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