In:
PLOS Biology, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2020-11-16), p. e3000943-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3000943
DOI:
10.1371/journal.pbio.3000943.g001
DOI:
10.1371/journal.pbio.3000943.g002
DOI:
10.1371/journal.pbio.3000943.g003
DOI:
10.1371/journal.pbio.3000943.g004
DOI:
10.1371/journal.pbio.3000943.g005
DOI:
10.1371/journal.pbio.3000943.g006
DOI:
10.1371/journal.pbio.3000943.s001
DOI:
10.1371/journal.pbio.3000943.s002
DOI:
10.1371/journal.pbio.3000943.s003
DOI:
10.1371/journal.pbio.3000943.s004
DOI:
10.1371/journal.pbio.3000943.s005
DOI:
10.1371/journal.pbio.3000943.s006
DOI:
10.1371/journal.pbio.3000943.s007
DOI:
10.1371/journal.pbio.3000943.s008
DOI:
10.1371/journal.pbio.3000943.s009
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2126773-X
Bookmarklink