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-a (FGF-2) and insulin-like growth factor-I (IGF-I) on oligodendrocytes and CNS myelination were determ ined in the postnatal rat anterior medullary velum (AMV) following injectio n of both cytokines into the cerebrospinal fluid. Either FGF-2, ICE-I, or s aline were administered via the lateral ventricle, twice daily commencing a t postnatal day (P) 6. At P9, AMV were immunohistochemically labeled with t he Rip antibody, to enable analysis of the numbers of myelin sheaths and of promyelinating and myelinating oligodendrocytes; promyelinating oligodendr ocytes are a recognisable immature phenotype which express myelin-related p roteins prior to forming myelin sheaths. In parallel experiments, AMV were treated for Western blot analysis to determine relative changes in expressi on of the myelin proteins 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP ) and myelin oligodendrocyte glycoprotein (MOG), which, respectively, chara cterise early and late stages of myelin maturation. In FGF-2-treated AMV, t he number of promyelinating oligodendrocytes increased by 87% compared to s aline-injected controls. The numbers of myelinating oligodendrocytes and my elin sheaths were not decreased, but conspicuous unmyelinated gaps within f ibre tracts were indications of retarded myelination following FGF-2 treatm ent. Western blot analysis demonstrated decreased expression of CNP and a n ear-total loss of MOG, confirming that FGF-2 decreased myelin maturation. I n contrast, IGF-I had no effect on the number of promyelinating oligodendro cytes, but increased the numbers of myelinating oligodendrocytes and myelin sheaths by 100% and 93%, respectively. Western blot analysis showed that t he amount of CNP was increased following IGF-I treatment, correlating with the greater number of oligodendrocytes, but that MOG expression was lower t han in controls, suggest ing 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 ICE-I control the numbers of oligodendrocyt es in the brain and, respectively, retard and promote myelination. (C) 1999 Wiley-Liss, Inc.