Myelination is altered in insulin-like growth factor-I null mutant mice.
Increasing evidence indicates that insulin-like growth factor-I (IGF-I) has an important role in oligodendrocyte development. In this study, we examined myelination during postnatal development in IGF-I knock-out (KO) mice by assessing myelin staining, the expression of myelin basic protein (MBP) and proteolipid protein (PLP), two major myelin-specific proteins, and the number of oligodendrocytes and their precursors. For comparison, we also measured the expression of median subunit of the neuron-specific intermediate filament, M-neurofilament (M-NF), to obtain an index of the effects of IGF-I deficiency on neurons. We found that myelin staining, MBP and PLP expression, and the percentage of oligodendrocytes and their precursors are significantly reduced in all brain regions of developing IGF-I KO mice but are similar to controls in adult IGF-I KO mice. In contrast, the abundance of M-NF was decreased in both the developing and adult brain of IGF-I KO mice. We also found that IGF-II protein abundance is increased in the brains of IGF-I KO mice. Our data indicate, therefore, that myelination during early development is altered in the absence of IGF-I by mechanisms that involve a reduction in oligodendrocyte proliferation and development. Although neuronal actions cannot be excluded in the myelin normalization, the reduced axonal growth suggested by the reduced M-NF expression makes a role for neuronal factors less compelling. These data suggest that IGF-I plays a significant role in myelination during normal early development and that IGF-II can compensate in part for IGF-I actions on myelination.
Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220, USA.
Ping
P
Ye
Liqin
L
Li
R Gregg
RG
Richards
Richard P
RP
DiAugustine
A Joseph
AJ
D'Ercole
D000375:Aging / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002452:Cell Count; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C061195:neurofilament protein M; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II