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2017 ; 15
(5
): e1002605
Nephropedia Template TP
Camargo N
; Goudriaan A
; van Deijk AF
; Otte WM
; Brouwers JF
; Lodder H
; Gutmann DH
; Nave KA
; Dijkhuizen RM
; Mansvelder HD
; Chrast R
; Smit AB
; Verheijen MHG
PLoS Biol
2017[May]; 15
(5
): e1002605
PMID28549068
show ga
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.