Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes

Ciliary neurotrophic factor (CNTF) is produced and released in response to injury in the central nervous system (CNS). While CNTF initially was characterized as a trophic factor for neurons, more recent evidence supports roles for this factor in survival, proliferation, and maturation of oligodendrocyte lineage cells. Evidence is emerging to support the hypothesis that CNTF's actions may include enhancing other growth and trophic factors. Here we tested the hypothesis that CNTF can induce expression of receptors on oligodendrocytes for factors that are known to promote their generation, maturation, and survival. Specifically, we used an in vivo paradigm to test whether CNTF, when injected stereotactically into forebrain white matter of adult rats, could induce mRNA expression for the insulin‐like growth factor (IGF) type I receptor (IGF‐IR), fibroblast growth factor (FGF) receptor (FGFR)‐1, FGFR3, and platelet‐derived growth factor (PDGF) receptor‐alpha (PDGFRα). We determined that CNTF injection increased expression of IGF‐IR and FGFR1 mRNAs in adult white matter to 200–250% of control levels. Cellular analysis indicated that these receptor mRNAs were induced in interfascicular oligodendrocytes. In contrast, CNTF had no effect on levels of FGFR3 and PDGFRα mRNAs. These results suggest that CNTF enhances the sensitivity of oligodendrocytes to other mitogens and trophic factors via induction of their receptors. J. Neurosci. Res. 57:447–457, 1999. © 1999 Wiley‐Liss, Inc.

[1]  A. Massaro.  Are there indicators of remyelination in blood or CSF of multiple sclerosis patients? , 1998, Multiple sclerosis.

[2]  R. Bansal,et al.  FGF‐2 converts mature oligodendrocytes to a novel phenotype , 1997, Journal of neuroscience research.

[3]  N. Oyesiku,et al.  Changes in expression of ciliary neurotrophic factor (CNTF) and CNTF-receptor alpha after spinal cord injury. , 1997, Journal of neurobiology.

[4]  D. Pleasure,et al.  Re‐entry into the cell cycle is required for bFGF‐induced oligodendroglial dedifferentiation and survival , 1996, Journal of neuroscience research.

[5]  N. Itoh,et al.  Distribution of and age‐related changes in ciliary neurotrophic factor protein in rat tissues , 1996, Biochemistry and molecular biology international.

[6]  S. Levison,et al.  Acute Exposure to CNTFin VivoInduces Multiple Components of Reactive Gliosis , 1996, Experimental Neurology.

[7]  H. Thoenen,et al.  Ciliary Neurotrophic Factor Enhances the Rate of Oligodendrocyte Generation , 1996, Molecular and Cellular Neuroscience.

[8]  R. Plunkett,et al.  Traumatized Rat Striatum Produces Neurite-Promoting and Neurotrophic Activitiesin Vitro , 1996, Experimental Neurology.

[9]  Madhur Kumar,et al.  Regulation of FGF Receptors in the Oligodendrocyte Lineage , 1996, Molecular and Cellular Neuroscience.

[10]  D. Compston,et al.  Growth factor stimulation triggers apoptotic cell death in mature oligodendrocytes , 1996, Journal of neuroscience research.

[11]  P. Gluckman,et al.  The effects of insulin-like growth factor (IGF)-1, IGF-2, and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats: evidence for a role for IGF binding proteins. , 1996, Endocrinology.

[12]  C. Heldin,et al.  Co‐localization of NG2 proteoglycan and PDGF α‐receptor on O2A progenitor cells in the developing rat brain , 1996, Journal of neuroscience research.

[13]  C. Heldin,et al.  Interaction between NG2 proteoglycan and PDGF α‐receptor on O2A progenitor cells is required for optimal response to PDGF , 1996, Journal of neuroscience research.

[14]  J. Antel,et al.  Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor‐mediated injury , 1996, Journal of neuroscience research.

[15]  F. Hefti,et al.  Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons , 1995, Neuron.

[16]  J. Vallat,et al.  Basic fibroblast growth factor down‐regulates myelin basic protein gene expression and alters myelin compaction of mature oligodendrocytes in vitro , 1995, Journal of neuroscience research.

[17]  S. Levison,et al.  Cytokines regulate IGF binding proteins in the cns. , 1995, Progress in growth factor research.

[18]  N. Ip,et al.  Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum , 1995, Journal of neuroscience research.

[19]  G. Yancopoulos,et al.  Neurotrophic Factor Receptors and Their Signal Transduction Capabilities in Rat Astrocytes , 1994, The European journal of neuroscience.

[20]  J. de Vellis,et al.  Platelet‐derived growth factor receptor is expressed by cells in the early oligodendrocyte lineage , 1994, Journal of neuroscience research.

[21]  M. Noble,et al.  Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. , 1994, Development.

[22]  D. Pleasure,et al.  Trophic effects of basic fibroblast growth factor (bFGF) on differentiated oligodendroglia: A mechanism for regeneration of the oligodendroglial lineage , 1993, Journal of neuroscience research.

[23]  S. Pfeiffer,et al.  Glial cell mitogens bFGF and PDGF differentially regulate development of O4+GalC- oligodendrocyte progenitors. , 1993, Developmental biology.

[24]  H. Thoenen,et al.  Disruption of the CNTF gene results in motor neuron degeneration , 1993, Nature.

[25]  J. Vallat,et al.  The proliferation of mature oligodendrocytes in vitro is stimulated by basic fibroblast growth factor and inhibited by oligodendrocyte-type 2 astrocyte precursors. , 1993, Developmental biology.

[26]  M. Carson,et al.  Regulation of Oligodendrocyte Development and Central Nervous System Myelination by Insulin‐like Growth Factors a , 1993, Annals of the New York Academy of Sciences.

[27]  B. Barres,et al.  Multiple extracellular signals are required for long-term oligodendrocyte survival. , 1993, Development.

[28]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in tTransgenic mice , 1993, Neuron.

[29]  Y. Kumon,et al.  Transient increase in endogenous basic fibroblast growth factor in neurons of ischemic rat brains , 1993, Brain Research.

[30]  S. Werner,et al.  Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. , 1993, Developmental biology.

[31]  J. Louis,et al.  CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death , 1993, Science.

[32]  S. Wiegand,et al.  Injury‐induced Regulation of Ciliary Neurotrophic Factor mRNA in the Adult Rat Brain , 1993, The European journal of neuroscience.

[33]  S. Frautschy,et al.  A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  W. Richardson,et al.  Cell death and control of cell survival in the oligodendrocyte lineage , 1992, Cell.

[35]  W. Richardson,et al.  PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. , 1992, Development.

[36]  E. Friedman,et al.  Pre-oligodendrocytes from adult human CNS , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  H. Webster,et al.  Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[38]  G. Yancopoulos,et al.  Ciliary neurotrophic factor and its receptor complex. , 1992, Progress in growth factor research.

[39]  S. Werner,et al.  Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. , 1992, Development.

[40]  R. Bunge,et al.  The origin of remyelinating cells in the adult central nervous system: The role of the mature oligodendrocyte , 1991, Glia.

[41]  T. Matsui,et al.  FGF modulates the PDGF-driven pathway of oligodendrocyte development , 1990, Neuron.

[42]  O. Bogler,et al.  Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[43]  H. Thoenen,et al.  Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor , 1989, Nature.

[44]  J. Lile,et al.  Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). , 1989, Science.

[45]  H. Werner,et al.  Developmental regulation of the rat insulin-like growth factor I receptor gene. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[46]  N. Ling,et al.  Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA. , 1988, Biochemical and biophysical research communications.

[47]  Thomas M. Smith,et al.  Insulin-like growth factor I/somatomedin C: a potent inducer of oligodendrocyte development. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[48]  C. Cotman,et al.  Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. , 1982, Science.

[49]  F. Greenwood,et al.  Preparation of Iodine-131 Labelled Human Growth Hormone of High Specific Activity , 1962, Nature.