Skip to main content
Log in

Expression of ubiquitin-like immunoreactivity in axons after compression trauma to rat spinal cord

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

The ubiquitin-mediated proteolytic pathway is an important mode of protein degradation in various tissues. Since breakdown of proteins may occur in axons after injury we evaluated the presence of ubiquitin-like immunoreactive material in rat spinal cord following compression injury of mild, moderate and severe degrees at T8-9 level, resulting in no neurological deficit, reversible paraparesis and paraplegia of the hind limbs, respectively. Rats with mild to severe compression injury surviving 1–4 days showed numerous, intensely immunoreactive expanded axons at the site of compression. The labelled axons were randomly distributed in the longitudinal tracts but they were never found in the corticospinal tracts. No labelling was detected by 9 days after injury. In addition, the presence of labelled axons was investigated in the T7 and the T10 segments from rats with moderate compression. No labelling was seen in T7, but in T10 segments many immunoreactive axons were present. Control rats did not show immunoreactive axons in the spinal cord. Neurons of dorsal root ganglia, trigeminal ganglia and of the grey matter of the spinal cord were immunoreactive. Cerebral cortical neurons did not show ubiquitin expression. Thus, compression of the rat spinal cord causes a transient accumulation of ubiquitin-like immunoreactive material in axonal swellings. Even though the dynamics of ubiquitin conjugates are not fully understood, the observed axonal accumulation presumably reflects arrested anterograde axonal transport of protein chiefly derived from neurons of dorsal root ganglia and the local neurons of the spinal cord. The presence of ubiquitin in damaged axons is one prerequisite for degradation of abnormal proteins by the ubiquitin-mediated proteolytic pathway, which may be activated in reactive axonal swellings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adams JH, Mitchell DE, Graham DI, Doyle D (1977) Diffuse brain damage of immediate impact type: its relationship to ‘primary brain-stem damage’ in head injury. Brain 100: 487–502

    Google Scholar 

  2. Adams JH, Graham DI, Murray LS, Scott G (1982) Diffuse axonal injury due to nonmissile head injury in humans. Ann Neurol 12: 557–563

    Article  PubMed  CAS  Google Scholar 

  3. Ahrens P, Besancon F, Memet S, Ankel H (1990) Tumour necrosis factor enhances induction by beta-interferon of a ubiquitin cross-reactive protein. J Gen Virol 71: 1675–1682

    Article  PubMed  CAS  Google Scholar 

  4. Balentine JD (1978) Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Lab Invest 39: 254–265

    PubMed  CAS  Google Scholar 

  5. Bizzi A, Schaetzle B, Patton A, Gambetti P, Autillo GL (1991) Axonal transport of the two major components of the ubiquitin system. Free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP9.5. Brain Res 548: 292–299

    Article  PubMed  CAS  Google Scholar 

  6. Bond V, Schlesinger MJ (1985) Ubiquitin is a heat shock protein in chicken embryo fibroblast. Mol Cell Biol 5: 949–956

    PubMed  CAS  Google Scholar 

  7. Bond V, Schlesinger MJ (1986) The chicken ubiquitin gene contains a heat shock promoter and expresses an unstable mRNA in heat shocked cells. Mol Cell Biol 6: 4602–4610

    PubMed  CAS  Google Scholar 

  8. Ciechanover A (1993) The ubiquitin-mediated proteolytic pathway. Brain Pathol 3: 67–75

    Article  PubMed  CAS  Google Scholar 

  9. Cochran E, Bacci B, Chen Y, Patton A, Gambetti P, Autilio-Gambetti L (1991) Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer’s disease. Am J Pathol 139: 485–489

    PubMed  CAS  Google Scholar 

  10. Dewar D, Graham D I, Teasdale G M, McCulloch J (1993) Alz-50 and ubiquitin immunoreactivity is induced by permanent focal cerebral ischaemia in the cat. Acta Neuropathol 86: 623–629

    Article  PubMed  CAS  Google Scholar 

  11. Finley D, Varshavsky A (1985) The ubiquitin system: functions and mechanisms. Trends Biochem Sci 10: 343–346

    Article  CAS  Google Scholar 

  12. Goldstein G, Sheid M, Hammerling U, Boyse EA, Schlesinger DH, Haill HD (1975) Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Natl Acad Sci USA 72: 11–15

    Article  PubMed  CAS  Google Scholar 

  13. Griffin JW, Price DL, Engel WK, Drachman DB (1977) The pathogenesis of reactive axonal swellings: role of axonal transport. J Neuropathol Exp Neurol 36: 214–227

    Article  PubMed  CAS  Google Scholar 

  14. Gultekin SH, Smith TW (1994) Diffuse axonal injury in craniocerebral trauma. A comparative histologic and immunohistochemical study. Arch Pathol Lab Med 118: 168–171

    PubMed  CAS  Google Scholar 

  15. Hershko A (1991) The ubiquitin pathway for protein degeneration. Trends Neurosci 16: 265–268

    CAS  Google Scholar 

  16. Hershko A, Ciechanover A (1986) The ubiquitin pathway for the degeneration of intracellular proteins. Prog Nucleic Acid Res Mol Biol 33: 19–56

    Article  PubMed  CAS  Google Scholar 

  17. Holtz A (1989) Spinal cord compression injury. Acta Univ Ups 209: 1–43

    Google Scholar 

  18. Lampert P (1967) A comparative electron microscopic study of reactive, degenerating, regenerating and dystrophic axons. J Neuropathol Exp Neurol 26: 345–368

    Article  PubMed  CAS  Google Scholar 

  19. Lanteri-Minet M, Desmeules JA, Menetrey D (1993) Opposite effects of axon damage on heat shock proteins (hsp 70) and ubiquitin contents in motor neurons of neuropathic rats. Neurosci Lett 153: 49–52

    Article  PubMed  CAS  Google Scholar 

  20. Li GL, Farooque M, Holtz A, Olsson Y (1995) Changes of B-amyloid precursor protein after compression trauma to the spinal cord: an experimental study in the rat using immunohis-tochemistry. J Neurotrauma 12: 269–277

    Article  PubMed  CAS  Google Scholar 

  21. Li GL, Farooque M, Holtz A, Olsson Y (1995) Microtubule-associated protein 2 as a sensitive marker for dendritic lesion after spinal cord trauma: an immunohistochemical study in the rat. Restor Neurol Neurosci 8:189–197

    CAS  Google Scholar 

  22. Loeb KR, Haas AL (1994) Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. Mol Cell Biol 14:8408–8419

    PubMed  CAS  Google Scholar 

  23. Lowe J, Mayer RJ (1990) Ubiquitin, cell stress and diseases of the nervous system. Neuropathol Appl Neurobiol 16: 281–291

    Article  PubMed  CAS  Google Scholar 

  24. Lowe J, Mayer RJ, Landon M (1993) Ubiquitin in neurodegenerative diseases. Brain Pathol 3: 55–65

    Article  PubMed  CAS  Google Scholar 

  25. Manetto V, Abdul-Karim FW, Perry G, Tabaton M, Autilio-Gambetti L, Gambetti P (1989) Selective presence of ubiquitin in intracellular inclusions. Am J Pathol 134: 505–513

    PubMed  CAS  Google Scholar 

  26. Martin JE, Mather KS, Swash M, Garofalo O, Dale GE, Leigh PN, Anderton BH (1990) Spinal cord trauma in man: studies of phosphorylated neurofilament and ubiquitin expression. Brain 113: 1553–1562

    Article  PubMed  Google Scholar 

  27. Mayer RJ, Lowe J, Landon M, McDermott H, Tuckwell J, Doherty F, Laszlo L (1991) Ubiquitin and the lysosome system: molecular immunopathology reveals the connection. Biomed Biochim Acta 50: 333–341

    PubMed  CAS  Google Scholar 

  28. Moretto G, Sparaco M, Monaco S, Bonetti B, Rizzuto N (1993) Cytoskeletal changes and ubiquitin expression in dystrophic axons of Seitelberger’s disease. Clin Neuropathol 12: 34–37

    PubMed  CAS  Google Scholar 

  29. Nystrom B, Berglund JE, Bergquist E (1988) Methodological analysis of an experimental spinal cord compression model in the rat. Acta Neurol Scand 78: 460–466

    Article  PubMed  CAS  Google Scholar 

  30. Oppenheimer DR (1968) Microscopic lesion in the brain following head injury. J Neurol Neurosurg Psychiatry 31: 299–306

    Article  PubMed  CAS  Google Scholar 

  31. Parag HA, Raboy B, Kulga RG (1987) Effect of heat shock on protein degradation in mammalian cells: involvement of the ubiquitin system. EMBO J 6: 55–61

    PubMed  CAS  Google Scholar 

  32. Peerless SJ, Rewcastle NB (1967) Shear injuries of the brain. Can Med Assoc J 96: 577–582

    PubMed  CAS  Google Scholar 

  33. Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci USA 84: 3033–3036

    Article  PubMed  CAS  Google Scholar 

  34. Povlishock JT (1993) Traumatic brain injury. The pathobiology of injury and repair. In: Gorio A (ed) Neuroregeneration. Raven Press, New York, pp 185–216

    Google Scholar 

  35. Povlishock JT, Becker DP (1985) Fate of reactive axonal swellings induced by head injury. Lab Invest 52: 540–552

    PubMed  CAS  Google Scholar 

  36. Povlishock JT, Becker DP, Cheng CLY, Vaughan GW (1983) Axonal change in minor head injury. J Neuropathol Exp Neurol 42: 225–242

    Article  PubMed  CAS  Google Scholar 

  37. Savedia S, Kiernan JA (1994) Increased production of ubiquitin mRNA in motor neurons after axotomy. Neuropathol Appl Neurobiol 20: 577–586

    Article  PubMed  CAS  Google Scholar 

  38. Schueler PA, Eide RP (1988) Differential expression of ubiquitin within the rat brain. Discretely localized increases following salt loading. J Chem Neuroanat 1: 165–175

    PubMed  CAS  Google Scholar 

  39. Schweitzer JB, Park MR, Einhaus SL, Robertson JT (1993) Ubiquitin marks the reactive swellings of diffuse axonal injury. Acta Neuropathol 85: 503–507

    Article  PubMed  CAS  Google Scholar 

  40. Sherriff FE, Bridges LR, Gentleman SM, Sivaloganathan S, Wilson S (1994) Markers of axonal injury in post mortem human brain. Acta Neuropathol 88: 433–439

    Article  PubMed  CAS  Google Scholar 

  41. Strich SJ (1961) Shearing of nerve fibers as a cause of brain damage due to head injury. Lancet II: 443–448

    Article  Google Scholar 

  42. Strich SJ (1970) The pathology of brain damage due to blunt head injuries. In: Walter AECW, Critchley M (eds) The late effects of head injury. Thomas, Springfield, pp 501–524

    Google Scholar 

  43. Tomlinson BE (1970) Brain-stem lesions after head injury. J Clin Pathol (Suppl) 4: 154–165

    Article  CAS  Google Scholar 

  44. Yaghmai A, Povlishock JT (1991) Traumatically induced reactive changes as visualized through the use of monoclonal antibodies targeted to the neurofilament subunits. J Neuropathol Exp Neurol 51: 158–176

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, G.L., Farooque, M. Expression of ubiquitin-like immunoreactivity in axons after compression trauma to rat spinal cord. Acta Neuropathol 91, 155–160 (1996). https://doi.org/10.1007/s004010050407

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s004010050407

Key words

Navigation