Duncan NRI Faculty and Staff Publications
Publication Date
10-1-2024
Journal
Nature Neuroscience
DOI
10.1038/s41593-024-01749-6
PMID
39251890
PMCID
PMC11452346
PubMedCentral® Posted Date
9-9-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Oligodendroglia, Energy Metabolism, Mice, Fatty Acids, Male, Female, Glucose, Mice, Inbred C57BL, Myelin Sheath, Glucose Transporter Type 1, Optic Nerve, Lipid Metabolism, Action Potentials, Adenosine Triphosphate, Astrocytes, Mitochondria, Mice, Transgenic, Central Nervous System, White Matter
Abstract
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.
Correction
Included in
Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons
Comments
This article has been corrected. See Nat Neurosci. 2024 Sep 17;27(10):2046.