Open AccessStructural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia
Author(s) -
Andrea Trevisiol,
Kathrin Kusch,
Anna M. Steyer,
Ingo Gregor,
Christos Nardis,
Ulrike Winkler,
Susanne Köhler,
Alejandro Restrepo,
Wiebke Möbius,
Hauke Werner,
KlausArmin Nave,
Johannes Hirrlinger
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000943
Subject(s) - biology , axon , myelin , neuroscience , oligodendrocyte , genetically modified mouse , microbiology and biotechnology , compound muscle action potential , axoplasmic transport , transgene , biochemistry , central nervous system , electrophysiology , gene
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 Plp null/y mouse model of spastic paraplegia. Optic nerves from Plp null/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 Plp null/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 Plp null/y mice.