A role for oligodendrocyte‐derived IGF‐1 in trophic support of cortical neurons

Neurons and glia interact in the development of mammalian central nervous systems and in the maintenance of stable myelinated axons. Recent evidence suggests a role for oligodendrocytes in providing trophic support for neurons during development and in the mature nervous system. This work prompted us to study oligodendrocyte influences on neuronal survival and death in vitro. Rat embryonic cortical neurons were co‐cultured with purified oligodendrocytes at different developmental stages and separately with oligodendrocyte‐conditioned medium. Neuronal survival was measured by immunocytochemistry and 3H‐GABA uptake. Neurons show a marked increase in survival when co‐cultured directly with oligodendrocyte precursors (OPCs) and differentiated oligodendrocytes. Neurons cultured in the presence of OPCs separated by a permeable membrane and those cultured in medium conditioned by oligodendrocytes also show a significant increase in survival. Medium conditioned by differentiated oligodendrocytes provides a greater survival effect than medium conditioned by OPCs. Neutralising antibodies to IGF‐1, but not to other candidate trophic factors, block the soluble survival effect of oligodendrocytes. Cells of the oligodendrocyte lineage produce IGF‐1 and recombinant IGF‐1 promotes neuronal survival under identical conditions. This study provides evidence that OPCs and differentiated oligodendrocytes support neuronal survival by both contact‐mediated and soluble mechanisms and that IGF‐1 significantly contributes to this effect. GLIA 36:48–57, 2001. © 2001 Wiley‐Liss, Inc.

[1]  G. Banker.  Trophic interactions between astroglial cells and hippocampal neurons in culture. , 1980, Science.

[2]  M. Tohyama,et al.  Roles of Bcl-2 and caspases in hypoxia-induced neuronal cell death: a possible neuroprotective mechanism of peptide growth factors. , 1998, Brain research. Molecular brain research.

[3]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[4]  S. Harper,et al.  The effects of insulin-like growth factor analogues on survival of cultured cerebral cortex and cerebellar granule neurones , 1996, Brain Research.

[5]  S. D’Mello,et al.  Insulin-Like Growth Factor and Potassium Depolarization Maintain Neuronal Survival by Distinct Pathways: Possible Involvement of PI 3-Kinase in IGF-1 Signaling , 1997, The Journal of Neuroscience.

[6]  H. Thoenen,et al.  Autocrine—paracrine Regulation of Hippocampal Neuron Survival by IGF‐1 and the Neurotrophins BDNF, NT‐3 and NT‐4 , 1996, The European journal of neuroscience.

[7]  David R. Kaplan,et al.  Regulation of Neuronal Survival by the Serine-Threonine Protein Kinase Akt , 1997, Science.

[8]  Y. Barde,et al.  Neurotrophins: a family of proteins supporting the survival of neurons. , 1994, Progress in clinical and biological research.

[9]  A. Campagnoni,et al.  Murine oligodendroglial cells express nerve growth factor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Brewer.  Serum‐free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus , 1995, Journal of neuroscience research.

[11]  D. Aunis,et al.  Chromogranin A induces a neurotoxic phenotype in brain microglial cells. , 1998, The Journal of biological chemistry.

[12]  C. M. Davenport,et al.  Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. , 1999, Science.

[13]  F. Mcmorris,et al.  Developing oligodendroglia express mRNA for insulin‐like growth factor‐I, a regulator of oligodendrocyte development , 1995, Journal of neuroscience research.

[14]  M. Raff,et al.  Effects of neonatal transection on glial cell development in the rat optic nerve: evidence that the oligodendrocyte-type 2 astrocyte cell lineage depends on axons for its survival , 1984, Journal of neurocytology.

[15]  W. Brück,et al.  Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. , 2000, Brain : a journal of neurology.

[16]  B. Barres,et al.  The relationship between neuronal survival and regeneration. , 2000, Annual review of neuroscience.

[17]  D. Riethmacher,et al.  Severe neuropathies in mice with targeted mutations in the ErbB3 receptor , 1997, Nature.

[18]  D. Kaplan,et al.  Akt-Dependent Potentiation of L Channels by Insulin-Like Growth Factor-1 Is Required for Neuronal Survival , 1999, The Journal of Neuroscience.

[19]  I. Duncan,et al.  Induction of sodium channel clustering by oligodendrocytes , 1997, Nature.

[20]  M. Tohyama,et al.  Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons , 1999, Journal of neurochemistry.

[21]  K. McCarthy,et al.  Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue , 1980, The Journal of cell biology.

[22]  V. Perry,et al.  Axonal damage in acute multiple sclerosis lesions. , 1997, Brain : a journal of neurology.

[23]  P M Matthews,et al.  In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis. , 1999, Brain : a journal of neurology.

[24]  D. Muir,et al.  CG‐4, A new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type‐2 astrocytes , 1992, Journal of neuroscience research.

[25]  M. Raff,et al.  Programmed Cell Death in Animal Development , 1997, Cell.

[26]  W. Snider,et al.  Functions of the neurotrophins during nervous system development: What the knockouts are teaching us , 1994, Cell.

[27]  Lawrence C Katz,et al.  Neurotrophin Regulation of Cortical Dendritic Growth Requires Activity , 1996, Neuron.

[28]  H. Neumann,et al.  Induction of MHC class I genes in neurons. , 1995, Science.

[29]  K. Unsicker,et al.  GDNF family members and their receptors: Expression and functions in two oligodendroglial cell lines representing distinct stages of oligodendroglial development , 1999, Glia.

[30]  M. Hanson,et al.  Depolarization and cAMP Elevation Rapidly Recruit TrkB to the Plasma Membrane of CNS Neurons , 1998, Neuron.

[31]  P. Canoll,et al.  GGF/Neuregulin Is a Neuronal Signal That Promotes the Proliferation and Survival and Inhibits the Differentiation of Oligodendrocyte Progenitors , 1996, Neuron.

[32]  M. Raff,et al.  A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium , 1983, Nature.

[33]  A. Meyer-Franke,et al.  Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture , 1995, Neuron.

[34]  D. Ferrari,et al.  Activation of microglial cells by β-amyloid protein and interferon-γ , 1995, Nature.

[35]  S. Pons,et al.  Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin‐like Growth Factor I , 1992, The European journal of neuroscience.

[36]  B. Barres,et al.  Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons , 1993, Nature.

[37]  M E Greenberg,et al.  Requirement for BDNF in activity-dependent survival of cortical neurons. , 1994, Science.

[38]  E. Feldman,et al.  Insulin‐like growth factor I rescues SH‐SY5Y human neuroblastoma cells from hyperosmotic induced programmed cell death , 1996, Journal of cellular physiology.

[39]  D. Raible,et al.  Regulation of Oligodendrocyte Development by Insulin‐Like Growth Factors and Cyclic Nucleotides a , 1990, Annals of the New York Academy of Sciences.

[40]  Yves-Alain Barde,et al.  Trophic factors and neuronal survival , 1989, Neuron.

[41]  Virginia M. Y. Lee,et al.  Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton , 1999, The Journal of Neuroscience.

[42]  R. Nixon,et al.  Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation , 1996, The Journal of Neuroscience.

[43]  A. Compston,et al.  Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis , 1999, Annals of neurology.

[44]  R. Reynolds,et al.  Uptake [3H]GABA by oligodendrocytes in dissociated brain cell culture: A combined autoradiographic and immunocytochemical study , 1984, Brain Research.

[45]  K. Nave,et al.  Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. , 1998, Science.

[46]  K. Fuxe,et al.  Modafinil prevents glutamate cytotoxicity in cultured cortical neurons , 1998, Neuroreport.

[47]  T. Takeshima,et al.  Oligodendrocyte-type-2 astrocyte (O-2A) progenitors increase the survival of rat mesencephalic, dopaminergic neurons from death induced by serum deprivation , 1994, Neuroscience Letters.

[48]  H. Ogura,et al.  Apoptotic Cell Death of Cultured Cerebral Cortical Neurons Induced by Withdrawal of Astroglial Trophic Support , 1998, Experimental Neurology.

[49]  A. Thompson,et al.  Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. , 1995, Brain : a journal of neurology.