TY - JOUR
T1 - Oligodendroglial myelination requires astrocyte-derived lipids
AU - Camargo, Nutabi
AU - Goudriaan, Andrea
AU - van Deijk, Anne-Lieke F
AU - Otte, Willem M.
AU - Brouwers, Jos F H M
AU - Lodder, Hans
AU - Gutmann, David H
AU - Nave, Klaus-Armin
AU - Dijkhuizen, Rick M.
AU - Mansvelder, Huibert D
AU - Chrast, Roman
AU - Smit, August B
AU - Verheijen, Mark H.G.
N1 - Publisher Copyright:
© 2017 Public Library of Science. All Rights Reserved.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/5/26
Y1 - 2017/5/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020170367&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.1002605
DO - 10.1371/journal.pbio.1002605
M3 - Article
C2 - 28549068
AN - SCOPUS:85020170367
SN - 1544-9173
VL - 15
JO - PLoS Biol
JF - PLoS Biol
IS - 5
M1 - e1002605
ER -