Format

Send to

Choose Destination
PLoS Biol. 2017 May 26;15(5):e1002605. doi: 10.1371/journal.pbio.1002605. eCollection 2017 May.

Oligodendroglial myelination requires astrocyte-derived lipids.

Author information

1
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
2
Biomedical MR Imaging and Spectroscopy group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, the Netherlands.
3
Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, the Netherlands.
5
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
6
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
7
Max-Planck-Institute of Experimental Medicine, Department of Neurogenetics, Goettingen, Germany.
8
Department of Neuroscience and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

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.

PMID:
28549068
PMCID:
PMC5446120
DOI:
10.1371/journal.pbio.1002605
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center