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

Abstract

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.