MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration
Open accessAbstract
Oligodendrocytes (OLs) are important for myelination and shuttling energy metabolites lactate and pyruvate toward axons through their expression of monocarboxylate transporter 1 (MCT1). Recent studies suggest that loss of OL MCT1 causes axonal degeneration. However, it is unknown how widespread and chronic loss of MCT1 in OLs specifically affects neuronal energy homeostasis with aging. To answer this, MCT1 conditional null mice were generated that allow for OL-specific MCT1 ablation. We observe that MCT1 loss from OL lineage cells is dispensable for normal myelination and axonal energy homeostasis early in life. By contrast, loss of OL lineage MCT1 expression with aging leads to significant axonal degeneration with concomitant hypomyelination. These data support the hypothesis that MCT1 is important for neuronal energy homeostasis in the aging central nervous system (CNS). The reduction in OL MCT1 that occurs with aging may enhance the risk for axonal degeneration and atrophy in neurodegenerative diseases.
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The model is in agreement with axonal degeneration observed in mice lacking the monocarboxylate transporter MCT1 in oligodendrocyte lineage cells.
“It is finally in agreement with axonal degeneration observed in mice lacking the monocarboxylate transporter MCT1 in oligodendrocytes lineage cells (Lee et al., 2012;Philips et al., 2021).”
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 Philips et al., 2021
Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters.
“Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters.”
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 Philips et al., 2021
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Cites
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“Mct1-tdTomato mice were generated in our laboratory and described in our earlier study (Lee et al., 2012).”
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“OLs appear to generate lactate and pyruvate in an activity-dependent manner: glutamate release from neurons activates NMDA receptors on OLs, increasing glucose uptake and lactate production through glycolysis (Saab et al., 2016).”
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- Authors
- Philips, T., Mironova, Y. A., Jouroukhin, Y., Chew, J., Vidensky, S., Farah, M. H., Pletnikov, M. V., Bergles, D. E., Morrison, B. M., & Rothstein, J. D.
- Affiliations
- Johns Hopkins University (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Morrison, Brett M.
- Rothstein, Jeffrey D.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 34
- Issue
- 2
- Pages
- 108610
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC8020895
- OpenAlex
- W3119484013
- Cited by
- 126
- References
- 5
- Citations by year
- 2026: 23 · 2025: 24 · 2024: 28 · 2023: 14 · 2022: 21 · 2021: 15 · 2020: 1
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke
- Amyotrophic Lateral Sclerosis Association
- National Institutes of Health
- Muscular Dystrophy Association (381190)
- Johns Hopkins University
- School of Medicine, Johns Hopkins University
- U.S. Department of Defense
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- MCT1, oligodendrocytes, hypomyelination, axonal degeneration, myelination, aging, neurodegeneration, axonal atrophy
- MeSH terms
- Monocarboxylate Transport Protein 1, Animals, Axons, Female, Male, Mice, Transgenic, Myelin Sheath, Nerve Degeneration, Oligodendroglia, Monocarboxylic Acid Transporters, Symporters, Mice
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