Chapter 1. The Role of Inhibitory Molecules in Limiting Axonal Regeneration in the Mammalian Spinal Cord

  1. Dr. Catherina G. Becker and
  2. Dr. Thomas Becker
  1. Patrick N. Anderson,
  2. Jez Fabes and
  3. David Hunt

Published Online: 5 FEB 2007

DOI: 10.1002/9783527610365.ch1

Model Organisms in Spinal Cord Regeneration

Model Organisms in Spinal Cord Regeneration

How to Cite

Anderson, P. N., Fabes, J. and Hunt, D. (2006) The Role of Inhibitory Molecules in Limiting Axonal Regeneration in the Mammalian Spinal Cord, in Model Organisms in Spinal Cord Regeneration (eds C. G. Becker and T. Becker), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527610365.ch1

Editor Information

  1. Centre for Neuroscience Research, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK

Author Information

  1. Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK

Publication History

  1. Published Online: 5 FEB 2007
  2. Published Print: 15 DEC 2006

ISBN Information

Print ISBN: 9783527315048

Online ISBN: 9783527610365

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Keywords:

  • CNS regeneration;
  • mammalian models;
  • mammalian spinal cord;
  • inhibitory molecules;
  • axonal regeneration;
  • axonal regeneration in the mammalian spinal cord;
  • inhibitors at the lesion site;
  • inhibitory signaling

Summary

This chapter contains sections titled:

  • Introduction

    • CNS Neurons Have Widely Differing Phenotypes

  • Difficulties in Assessing Axonal Regeneration in the Mammalian Spinal Cord

    • Experimental Lesions and Problems of Interpretation

    • Tracing Regenerating Axons

      • Regeneration of Corticospinal Axons is Difficult to Assess

      • Regeneration of Ascending Dorsal Column Axons Can Be Measured Simply and Accurately

  • Myelin Proteins as Inhibitors of Axonal Regeneration

    • Nogo

    • OMgp

    • MAG

    • The Nogo-66 Receptor, NgR1, (RTN4R), and Related Molecules

    • Co-Receptors: LINGO-1, p75 and TROY (TAJ)

    • Signal Transduction from Myelin-Derived Inhibitory Molecules

    • The Role of Nogo-A in Axonal Regeneration in the Spinal Cord

      • Variations in the Extent of Axonal Regeneration in Different Strains of Nogo Knockout Mice

      • Effects of Antibodies Against Nogo on Axonal Regeneration in Spinal Cord

      • Neuronal Nogo-A

    • The Role of NgR1, NgR2 and Their Co-Receptors in Axonal Regeneration Within the Spinal Cord

      • The Distribution of NgR1 and NgR2 Does Not Suggest a General Regeneration-Inhibitory Function in the CNS

      • Knockout Mice Do Not Provide a Clear Picture of the Role of NgR1 in Regeneration

      • Pharmacological Blockade of NgR1 Enhances Axonal Sprouting and Regeneration

      • The Pattern of Expression of LINGO-1 and p75 Does Not Suggest a General Role in Inhibiting Regeneration in Vivo

      • LINGO-1, p75 and TROY Have Important Roles in Neurite Outgrowth in Vitro, But Their Significance for Axonal Regeneration in Vivo Has Not Yet Been Established

    • Effects of MAG and OMgp on Axon Regeneration in the Mammalian CNS

    • Strong Evidence That Myelin Proteins Are Not Always Effective Inhibitors of Axonal Regeneration in Vivo

  • Inhibitors at the Lesion Site

    • CSPGs

      • Relationship Between the Distribution of CSPGs and Failure of Axonal Regeneration

      • Chondroitinase ABC and Axonal Regeneration

      • Scar-Reducing and Growth-Promoting Effects of Decorin

    • Axonal Guidance Molecules Are Present in the Spinal Cord and Their Receptors Are Expressed by Specific Classes of Neuron

      • Semaphorins

      • Ephrins

      • Slits and Netrins in the Mammalian Spinal Cord

  • The Most Consistent Effects of Interfering with Inhibitory Molecules or Their Signaling Are on Raphespinal Axons

  • Interfering with Downstream Effectors of Inhibitory Signaling

    • Cyclic AMP Can Modulate the Responses of Neurons to Inhibitory Molecules in Vitro But is Only a Weak Promoter of Axonal Regeneration in the Spinal Cord

    • Rho-A Inhibition

    • Interfering with Other Targets on Signaling Pathways

  • Inhibitory Molecules and the Control of Neuronal Growth-Associated Genes

  • Conclusions