Structural and functional alterations of spinal cord axons in adult Long Evans Shaker (LES) dysmyelinated rats

Exp Neurol. 2005 Jun;193(2):334-49. doi: 10.1016/j.expneurol.2005.01.019.


Abnormal formation or loss of myelin is a distinguishing feature of many neurological disorders and contributes to the pathobiology of neurotrauma. In this study we characterize the functional and molecular changes in CNS white matter in Long Evans Shaker (LES) rats. These rats have a spontaneous mutation of the gene encoding myelin basic protein which results in severe dysmyelination of the central nervous system (CNS), providing a unique model for demyelinating/dysmyelinating disorders. To date, the functional and molecular changes in CNS white matter in this model are not well understood. We have used in vivo somatosensory evoked potential (SSEP), in vitro compound action potential (CAP) recording in isolated dorsal columns, confocal immunohistochemistry, Western blotting and real-time PCR to examine the electrophysiological, molecular and cellular changes in spinal cord white matter in LES rats. We observed that dysmyelination is associated with dispersed labeling of Kv1.1 and Kv1.2 K+ channel subunits, as well as Caspr, a protein normally confined to paranodes, along the LES rat spinal cord axons. Abnormal electrophysiological properties including attenuation of CAP amplitude and conduction velocity, high frequency conduction failure and enhanced sensitivity to K+ channel blockers 4-aminopyridine and dendrotoxin-I were observed in spinal cord axons from LES rats. Our results in LES rats clarify some of the key molecular, cellular and functional consequences of dysmyelination and myelin-axon interactions. Further understanding of these issues in this model could provide critical insights for neurological disorders characterized by demyelination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Action Potentials / radiation effects
  • Analysis of Variance
  • Animals
  • Axons / metabolism*
  • Axons / physiology*
  • Blotting, Western / methods
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Evoked Potentials, Somatosensory / physiology
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Kv1.1 Potassium Channel
  • Kv1.2 Potassium Channel
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Neural Conduction / physiology
  • Neural Conduction / radiation effects
  • Neurofilament Proteins / metabolism
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • Pyrimidines / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Long-Evans
  • Rats, Mutant Strains / genetics
  • Rats, Mutant Strains / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology*
  • Spinal Cord / radiation effects


  • Cell Adhesion Molecules, Neuronal
  • Cntnap1 protein, rat
  • Kcna2 protein, rat
  • Kv1.2 Potassium Channel
  • Myelin Basic Protein
  • Neurofilament Proteins
  • Peptides
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Pyrimidines
  • RNA, Messenger
  • neurofilament protein H
  • dendrotoxin K
  • Kv1.1 Potassium Channel
  • 4-aminopyrimidine