Regulation of Oligodendrocyte Development and Myelination by Glucose and Lactate
Open accessAbstract
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 express GFP (green fluorescent protein) under the control of the Sox10 promoter, we show 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.
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During developmental myelination, oligodendrocytes import and utilize lactate for ATP generation and the synthesis of myelin lipids, which requires functional expression of LDH.
“During developmental myelination, oligodendrocytes are thought to import and utilize lactate for ATP generation and the synthesis of myelin lipids (Amaral et al., 2016;Rinholm et al., 2011;Sánchez-Abarca et al., 2001), which requires functional expression of LDH.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Rinholm et al., 2011
The Introduction says oligodendrocytes need ATP and lipids for myelination and reports that cultured oligodendrocytes use lactate to fuel mitochondria and synthesize lipids. The Discussion confirms lactate uptake and shows that added lactate supports myelination under low-glucose conditions. The cited paper does not establish the added claim that this requires functional LDH expression. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCultured oligodendrocytes in vitro express both LDHA and LDHB.
“we detected both LDHA and LDHB in these cells in vitro.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Rinholm et al., 2011
The Results section on cultured cortical slices reports myelination and lactate responses, but not LDHA or LDHB expression. Searches for LDHA, LDHB, and lactate dehydrogenase isoforms found no passage in our copy establishing that cultured oligodendrocytes express both. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Cites
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Self-citation
- Authors
- Rinholm, J. E., Hamilton, N. B., Kessaris, N., Richardson, W. D., Bergersen, L. H., & Attwell, D.
- Affiliations
- University College London (GB)
- University of Oslo (NO)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-01-12
- Volume
- 31
- Issue
- 2
- Pages
- 538-548
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3044866
- OpenAlex
- W2038392123
- Cited by
- 383
- References
- 4
- Citations by year
- 2026: 28 · 2025: 21 · 2024: 34 · 2023: 27 · 2022: 32 · 2021: 22 · 2020: 23 · 2019: 22 · 2018: 20 · 2017: 27 · 2016: 32 · 2015: 22 · 2014: 27 · 2013: 24 · 2012: 13
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (080513, 075232/Z/04/Z)
- European Commission
- Universitetet i Oslo
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- oligodendrocyte development, myelination, lactate, glucose, monocarboxylate transporters, MCT1, lactate transport, oligodendrocyte lineage, cortical development, energy deprivation, remyelination, periventricular leukomalacia, white matter, cerebellum, corpus callosum, SOX10
- MeSH terms
- Monocarboxylate Transport Protein 1, Animals, Brain, Cerebral Cortex, Glucose, Hydrogen-Ion Concentration, Male, Mice, Transgenic, Myelin Sheath, Oligodendroglia, Rats, Sprague-Dawley, Rats, Wistar, Patch-Clamp Techniques, Lactic Acid, Monocarboxylic Acid Transporters, Symporters, Tissue Culture Techniques, Mice, Rats
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