Oligodendroglial fatty acid metabolism as a central nervous system energy reserve.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
09 Sep 2024
09 Sep 2024
Historique:
received:
22
06
2023
accepted:
05
08
2024
medline:
10
9
2024
pubmed:
10
9
2024
entrez:
9
9
2024
Statut:
aheadofprint
Résumé
Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease.
Identifiants
pubmed: 39251890
doi: 10.1038/s41593-024-01749-6
pii: 10.1038/s41593-024-01749-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SPP1757
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR-274
Informations de copyright
© 2024. The Author(s).
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