Oligodendroglial myelination requires astrocyte-derived lipids
Open accessAbstract
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age. Importantly, embryonic deletion of the same gene in astrocytes, or in astrocytes and oligodendrocytes, caused a persistent hypomyelination, as did deletion from astrocytes during postnatal development. Moreover, when astroglial lipid synthesis was inhibited, oligodendrocytes began incorporating circulating lipids into myelin membranes. Indeed, a lipid-enriched diet was sufficient to rescue hypomyelination in these conditional mouse mutants. We conclude that lipid synthesis by oligodendrocytes is heavily supplemented by astrocytes in vivo and that horizontal lipid flux is a major feature of normal brain development and myelination.
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Astrocyte-derived cholesterol is an essential supplement to oligodendrocytes during myelination in normal development.
“Astrocyte-derived cholesterol is an essential supplement to OLs during myelination in normal development (Camargo et al. 2017;Werkman et al. 2021)”
From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Camargo et al. 2017
The Abstract (page not provided) says astrocytes substantially supplement oligodendrocyte lipid synthesis during normal brain development. The Discussion, under “Involvement of astrocyte lipid metabolism in myelin membrane synthesis” (page not provided), notes that cholesterol synthesis occurs mainly in astrocytes after peak myelination. The paper does not establish that astrocyte-derived cholesterol, specifically, is the essential supplement rather than astrocyte-derived lipids more broadly. (LLM, conf=0.84)
Experimental — accuracy not yet measuredWhen lipid synthesis in OL declines with age, myelin maintenance becomes reliant on astrocyte-derived lipid supply.
“When lipid synthesis in OL declines with age, myelin maintenance become reliant on astrocyte-derived lipids supply (Dimas et al. 2019;Saher et al. 2005;Camargo et al. 2017).”
From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Camargo et al. 2017
The Discussion says oligodendrocytes produce much cholesterol at the peak of myelination, whereas synthesis occurs mainly in astrocytes thereafter; it also reports that astrocyte lipid supply is needed for full myelin membrane synthesis. These passages concern later-stage myelination, not an age-related decline in oligodendrocyte lipid synthesis or a demonstrated dependence of myelin maintenance on astrocytes. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Glial Cells Promote Myelin Formation and Elimination
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A perspective on astrocyte regulation of neural circuit function and animal behavior
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- Authors
- Camargo, N., Goudriaan, A., van Deijk, A.-L. F., Otte, W. M., Brouwers, J. F., Lodder, H., Gutmann, D. H., Nave, K.-A., Dijkhuizen, R. M., Mansvelder, H. D., Chrast, R., Smit, A. B., & Verheijen, M. H. G.
- Affiliations
- Amsterdam Neuroscience (NL)
- University Medical Center Utrecht (NL)
- Utrecht University (NL)
- Washington University in St. Louis (US)
- Max Planck Institute of Experimental Medicine (DE)
- Karolinska Institutet (SE)
- Corresponding author
- Verheijen, Mark H. G.
- ORCID
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-05-26
- Volume
- 15
- Issue
- 5
- Pages
- e1002605
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC5446120
- OpenAlex
- W2619465759
- Cited by
- 296
- References
- 48
- Citations by year
- 2026: 36 · 2025: 44 · 2024: 30 · 2023: 37 · 2022: 42 · 2021: 32 · 2020: 37 · 2019: 21 · 2018: 12 · 2017: 5
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- PLoS Biology (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, public-domain)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Universiteit Utrecht
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- myelination, oligodendrocytes, astrocytes, myelin lipids, lipid transfer, SCAP, hypomyelination, lipogenesis, brain development
- MeSH terms
- Animals, Astrocytes, Crosses, Genetic, Demyelinating Diseases, Glial Fibrillary Acidic Protein, Humans, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Myelin Sheath, Nerve Tissue Proteins, Oligodendroglia, Organ Specificity, Protein Processing, Post-Translational, Biomarkers, Gene Deletion, Microscopy, Electron, Transmission, Intracellular Signaling Peptides and Proteins, Lipid Metabolism, Sterol Regulatory Element Binding Protein 2, Fatty Acid Synthase, Type I, Diet, High-Fat
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