In vivo actions of fibroblast growth factor-2 and insulin-like growth factor-I on oligodendrocyte development and myelination in the central nervous system.
The in vivo effects of fibroblast growth factor-2 (FGF-2) and insulin-like growth factor-I (IGF-I) on oligodendrocytes and CNS myelination were determined in the postnatal rat anterior medullary velum (AMV) following injection of both cytokines into the cerebrospinal fluid. Either FGF-2, IGF-I, or saline were administered via the lateral ventricle, twice daily commencing at postnatal day (P) 6. At P9, AMV were immunohistochemically labeled with the Rip antibody, to enable analysis of the numbers of myelin sheaths and of promyelinating and myelinating oligodendrocytes; promyelinating oligodendrocytes are a recognisable immature phenotype which express myelin-related proteins prior to forming myelin sheaths. In parallel experiments, AMV were treated for Western blot analysis to determine relative changes in expression of the myelin proteins 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and myelin oligodendrocyte glycoprotein (MOG), which, respectively, characterise early and late stages of myelin maturation. In FGF-2-treated AMV, the number of promyelinating oligodendrocytes increased by 87% compared to saline-injected controls. The numbers of myelinating oligodendrocytes and myelin sheaths were not decreased, but conspicuous unmyelinated gaps within fibre tracts were indications of retarded myelination following FGF-2 treatment. Western blot analysis demonstrated decreased expression of CNP and a near-total loss of MOG, confirming that FGF-2 decreased myelin maturation. In contrast, IGF-I had no effect on the number of promyelinating oligodendrocytes, but increased the numbers of myelinating oligodendrocytes and myelin sheaths by 100% and 93%, respectively. Western blot analysis showed that the amount of CNP was increased following IGF-I treatment, correlating with the greater number of oligodendrocytes, but that MOG expression was lower than in controls, suggesting that the increased number of myelin sheaths in IGF-I was not matched by increased myelin maturation. The results provide in vivo evidence that FGF-2 and IGF-I control the numbers of oligodendrocytes in the brain and, respectively, retard and promote myelination.
Goddard
D R
DR
Division of Physiology, Guy's King's and St. Thomas' School of Biomedical Sciences, King's College, London, England.
Berry
M
M
Butt
A M
AM
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D011149:Pons / Q000166:cytology / Q000254:growth & development*; D051381:Rats; D017208:Rats, Wistar
D004676:Myelin Basic Protein; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I