Progressive changes in neurofilament proteins and growth-associated protein-43 immunoreactivities at the site of cervical spinal cord compression in spinal hyperostotic mice

Spine (Phila Pa 1976). 2002 Mar 1;27(5):480-6. doi: 10.1097/00007632-200203010-00008.

Abstract

Study design: Immunohistochemical examination of the expression and localization of neurofilament (NF) proteins and growth-associated protein (GAP)-43 in spinal hyperostotic (twy/twy) mice with progressive compression of the cervical spinal cord.

Objective: To determine the biologic functions of NF proteins and GAP-43 in the mouse cervical spinal cord during chronic mechanical compression.

Summary of background data: The pathologic and repair process in the chronically compressed spinal cord are understood poorly. The present authors hypothesized that there existed an increased expression of NF proteins and GAP-43 in twy/twy mice during the lengthy period of spinal cord compression, which resembles compressive myelopathy.

Methods: The cervical spinal cords of 54 twy mice (aged 8 weeks [n = 18], 14 weeks [n = 18], and 20 weeks [n = 18]) and 18 control animals were examined histologically. Using appropriate antibodies, sections were also stained immunohistochemically for NF proteins and GAP-43.

Results: Separation of the myelin sheath from the axon and axonal swelling with deformation were detected in the anterior and lateral funiculi of the spinalcords of 20-week-old twy/twy mice. No such changes were noted in 8-week-old twy mice. In twy/twy mice aged 8 and 14 weeks with mild-to-moderate compression, weak immunoreactivities (mainly in the white matter) for NF proteins and GAP-43 were noted; however, in 20-week-old twy/twy mice, these axons stained strongly positive and immunoreactive swollen axons were present. The relative area of GAP-43 immunoreactive axons gradually increased between 8 and 20 weeks in each column, particularly in the anterior and lateral funiculi in the contralateral side of compression.

Conclusions: The results showed that the expression of NF proteins and GAP-43 in the white matter increased proportionally with the magnitude of spinal cord compression, and indicated the possible involvement of GAP-43 in both axonal degeneration and repair processes in the chronically compressed spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Disease Models, Animal
  • Disease Progression
  • GAP-43 Protein / metabolism*
  • Genetic Predisposition to Disease
  • Hyperostosis* / complications
  • Hyperostosis* / genetics
  • Immunohistochemistry
  • Mice
  • Mice, Inbred ICR
  • Mice, Inbred Strains
  • Neck
  • Nerve Fibers, Myelinated / pathology
  • Neurofilament Proteins / metabolism*
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • Spinal Cord Compression / etiology
  • Spinal Cord Compression / metabolism*
  • Spinal Cord Compression / pathology

Substances

  • GAP-43 Protein
  • Neurofilament Proteins