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Journal of Neuroscience, Vol 15, 7344-7356, Copyright © 1995 by Society for Neuroscience
In vivo actions of insulin-like growth factor-I (IGF-I) on brain myelination: studies of IGF-I and IGF binding protein-1 (IGFBP-1) transgenic mice
P Ye, J Carson and AJ D'Ercole
Department of Pediatrics, University of North Carolina at Chapel Hill 27599-7220, USA.
To study the effects and mechanisms of insulin-like growth factor I (IGF-I)
on brain myelination in vivo, the morphology of myelinated axons and the
expression of myelin specific protein genes have been examined in
transgenic (Tg) mice that overexpress IGF-I and that those ectopically
express IGF binding protein-1 (IGFBP-1), a protein that inhibits IGF-I
actions when present in molar excess. Our data show that the percentage of
myelinated axons and the thickness of myelin sheaths are significantly
increased in IGF-I Tg and decreased in the IGFBP-1 mice. Cerebral cortical
proteolipid protein (PLP) and myelin basic protein (MBP) mRNAs consistently
exhibit approximately 200% increases in IGF-I Tg mice and approximately 50%
decreases in IGFBP-1 Tg mice. The percentage of oligodendrocytes labeled
with a PLP cRNA probe in the corpus callosum and cerebral cortex also is
increased in IGF-I Tg mice and reduced in IGFBP-1 Tg mice, suggesting that
IGF-I promotes oligodendrocyte survival and/or proliferation. The
alterations in the number of oligodendrocytes, however, can not completely
account for the changes in myelin gene expression. These results strongly
indicate that IGF-I increases myelination by increasing the number of
myelinated axons and the thickness of myelin sheaths, the latter by
mechanisms that involve stimulation of the expression of myelin protein
genes and increase of oligodendrocyte number.
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