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- Title
Regulation of Oligodendrocyte Development and Myelination by Glucose and Lactate.
- Authors
Rinholm, Johanne E.; Hamilton, Nicola B.; Kessaris, Nicoletta; Richardson, William D.; Bergersen, Linda H.; Attwell, David
- Abstract
In the gray matter of the brain, astrocytes have been suggested to export lactate (derived from glucose or glycogen) to neurons to power their mitochondria. In the white matter, lactate can support axon function in conditions of energy deprivation, but it is not known whether lactate acts by preserving energy levels in axons or in oligodendrocytes, the myelinating processes of which are damaged rapidly in low energy conditions. Studies of cultured cells suggest that oligodendrocytes are the cell type in the brain that consumes lactate at the highest rate, in part to produce membrane lipids presumably for myelin. Here, we use pH imaging to show that oligodendrocytes in the white matter of the rat cerebellum and corpus callosum take up lactate via monocarboxylate transporters (MCTs), which we identify as MCT1 by confocal immunofluorescence and electron microscopy. Using cultured slices of developing cerebral cortex from mice in which oligodendrocyte lineage cells expressGFP(green fluorescent protein) under the control of the Sox10 promoter,weshow that a low glucose concentration reduces the number of oligodendrocyte lineage cells and myelination. Myelination is rescued when exogenous L-lactate is supplied. Thus, lactate can support oligodendrocyte development and myelination. In CNS diseases involving energy deprivation at times of myelination or remyelination, such as periventricular leukomalacia leading to cerebral palsy, stroke, and secondary ischemia after spinal cord injury, lactate transporters in oligodendrocytes may play an important role in minimizing the inhibition of myelination that occurs.
- Subjects
OLIGODENDROGLIA; REGULATION of secretion; MYELINATION; IMMUNOFLUORESCENCE; GLUCOSE; LACTATES; LABORATORY rats
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 2, p538
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3516-10.2011