Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia.
Action Potentials
Adenosine Triphosphate
/ metabolism
Animals
Axons
/ metabolism
Disease Models, Animal
Energy Metabolism
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Myelin Proteolipid Protein
/ deficiency
Myelin Sheath
/ metabolism
Optic Nerve
/ metabolism
Paraplegia
/ genetics
Phenotype
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
24
02
2020
accepted:
22
10
2020
revised:
30
11
2020
pubmed:
17
11
2020
medline:
5
1
2021
entrez:
16
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33196637
doi: 10.1371/journal.pbio.3000943
pii: PBIOLOGY-D-20-00471
pmc: PMC7704050
doi:
Substances chimiques
Myelin Proteolipid Protein
0
Plp1 protein, mouse
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000943Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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