Advertisement

Journal of Neurocytology

, Volume 28, Issue 7, pp 559–570 | Cite as

Glial cell responses, complement and apolipoprotein J expression following axon injury in the neonatal rat

  • Ran Tao
  • Håkan Aldskogius
Article

Abstract

Immature motoneurons are highly susceptible to degeneration following axon injury. The response of perineuronal glia to axon injury may significantly influence neuronal survival and axon regeneration. We have examined the central reactions to neonatal facial nerve transection with emphasis on the expression of complement component C3 (C3) and the multifunctional apolipoprotein J (ApoJ). Axotomy was performed on one-day-old rats. Animals were perfused from eight hours to two weeks after the lesion. The astroglial marker, glial fibrillary acidic protein (GFAP) was increased from one day and the microglial marker OX-42 from two days after injury. ApoJ immunoreactivity was increased in axotomized neuronal perikarya and astroglial cells from one day postaxotomy, but no C3 immunoreactive profiles were found at any postoperative survival time. Cell proliferation as judged by bromodeoxyuridine labeling and immunoreactivity for the cyclin Ki-67 antigen (antibody MIB5) occurred only at two days after injury. Double immunostaining revealed that the vast majority of proliferating cells were microglia, although occasional cells double labeled astrocytes were found as well. Our results indicate that the non-neuronal response in neonatal animals differ from that of adult ones as follows: 1) microglia transform rapidly into phagocytes in parallel with the degeneration of axotomized neurons, 2) despite the presence of neuronal degeneration, no expression of C3 was found, and the upregulation of the expression of the complement C3 receptor (CR3) is delayed, 3) ApoJ is strongly upregulated in perineuronal astrocytes as well as in the axotomized motoneurons. The marked upregulation of ApoJ in both instances suggests a general role of this protein in the neuronal response to axotomy.

Keywords

Glial Fibrillary Acidic Protein Nerve Transection Microglial Marker Neuronal Perikaryon Antibody MIB5 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adel Moallem, S. & Hales, B. F. (1996) Transglutaminase and clusterin induction during normal and abnormal limb development in the mouse. Biology of Reproduction 55, 281–290.Google Scholar
  2. Aldskogius, H. (1974) Indirect and direct Wallerian degeneration in the intramedullary root fibres of the hypoglossal nerve. Advances in Anatomy, Embryology and Cell Biology 50, 1–78.Google Scholar
  3. Aldskogius, H. & Svensson, M. (1993) Neuronal and glial cell responses to axon injury. In Advances in Structural Biology, Vol. 2 (edited by MALHOTRA, S. K.), pp. 191–223. Greenwich, Conn: JAI Press.Google Scholar
  4. Aldskogius, H. & Kozlova, E. N. (1998) Central neuron-glial and glial-glial interactions following axon injury. Progress in Neurobiology 54, 1–26.Google Scholar
  5. Balasingam, V., Dickson, K., Brade, A. & Yong, V. W. (1996) Astrocyte reactivity in neonatal mice: apparent dependence on the presence of reactive microglia/macrophages. Glia 18, 11–26.Google Scholar
  6. Bray, G. M., Villegas Perez, M. P., Vidal Sanz, M. & Aguayo, A. J. (1987) The use of peripheral nerve grafts to enhance neuronal survival, promote growth and permit terminal reconnections in the central nervous system of adult rats. Journal of Experimental Biology 132, 5–19.Google Scholar
  7. Bursch, W., Gleeson, T., Kleine, L. & Tenniswood, M. (1995) Expression of clusterin (testosterone-repressed prostate message-2) mRNA during growth and regeneration of rat liver. Archives of Toxicology 69, 253–258.Google Scholar
  8. Chao, C. C., Hu, S. & Peterson, P. K. (1995) Glia, cytokines and neurotoxicity. Critical Reviews in Neurobiology 9, 189–205.Google Scholar
  9. Damoiseaux, J. G., Dopp, E. A., Calame, W., Chao, D., Macpherson, G. G. & Dijkstra, C. D. (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83, 140–147.Google Scholar
  10. Danik, M., Chabot, J. G., Hassan Gonzalez, D., Suh, M. & Quirion, R. (1993) Localization of sulfated Complement and ApoJ in neonatal rat 569 glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization. Journal of Comparative Neurology 334, 209–227.Google Scholar
  11. De Vries, H., De Jonge, J. C., Schrage, C., Van Dper Haar, M. E. & Hoekstra, D. (1997) Differential and cell development-dependent localization of myelin mRNAs in oligodendrocytes. Journal of Neuroscience Research 47, 479–488.Google Scholar
  12. Foster, P. N. & Trejdosiewicz, L. K. (1992) Impaired proliferative responses of peripheral blood B cells from splenectomized subjects to phorbol ester and ionophore [see comments]. Clinical and Experimental Immunology 89, 369–373.Google Scholar
  13. Garden, G. A., Bothwell, M. & Rubel, E. W. (1991) Lack of correspondence between mRNA expression for a putative cell death molecule (SGP-2) and neuronal cell death in the central nervous system. Journal of Neurobiology 22, 590–604.Google Scholar
  14. Giulian, D., Li, J., Li, X., George, J. & Rutecki, P. A. (1994) The impact of microglia-derived cytokines upon gliosis in the CNS. Developmental Neuroscience 16, 128–136.Google Scholar
  15. Graeber, M. B, LÓpez-Redondo, F., Ikoma, E., Ishikawa, M., Imai, Y., Nakajima, K., Kreutzberg, G. W. & Kohsaka, S. (1998) The microglia/macrophage response in the neonatal rat facial nucleus following axotomy. Brain Research 813, 241–253.Google Scholar
  16. Graeber, M. B., Tetzlaff, W., Streit, W. J. & Kreutzberg, G. W. (1988) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neuroscience Letters 85, 317–321.Google Scholar
  17. Greensmith, L., Mentis, G. Z. & Vrbova, G. (1994) Blockade of N-methyl-D-aspartate receptors by MK-801 (dizocilpine maleate) rescues motoneurones in developing rats. Developmental Brain Research 81, 162–170.Google Scholar
  18. Guenette, R. S. & Tenniswood, M. (1994) The role of growth factors in the suppression of active cell death in the prostate: an hypothesis. Biochemistry and Cell Biology 72, 553–559.Google Scholar
  19. Hall, E. D., Smith, S. L. & Oostveen, J. A. (1996) 0Inhibition of lipid peroxidation attenuates axotomy-induced apoptotic degeneration of facial motor neurons in neonatal rats. Journal of Neuroscience Research 44, 293–299.Google Scholar
  20. He, B. P., Tay, S. S. & Leong, S. K. (1997a) Microglia responses in the CNS following sciatic nerve transection in C57BL/Wld(s) and BALB/c mice. Experimental Neurology 146, 587–595.Google Scholar
  21. He, B. P., Tay, S. S. & Leong, S. K. (1997b) Do microglial cells have a neuroprotective function? Journal f ¬ur Hirnforschung 38, 309–315.Google Scholar
  22. Koch Brandt, C. & Morgans, C. (1996) Clusterin: a role in cell survival in the face of apoptosis? Progress in Molecular and Subcellular Biology 16, 130–149.Google Scholar
  23. Lieberman, A. R. (1971) The axon reaction: a review of the principal features of perikaryal responses to axon injury. International Reviews of Neurobiology 14, 49–124.Google Scholar
  24. Lieberman, A. R. (1974) Some factors affecting retrograde neuronal responses to axonal lesions. In Essays on the Nervous System (edited by Bellairs, R. & Gray, E. G.), pp. 71–105. Oxford: Clarendon.Google Scholar
  25. Liu, L., TÖrnqvist, E., Mattsson, P., Eriksson, N. P., Persson, J. K., Morgan, B. P., Aldskogius, H. & Svensson, M. (1995) Complement and clusterin in the spinal cord dorsal horn and gracile nucleus following sciatic nerve injury in the adult rat. Neuroscience 68, 167–179.Google Scholar
  26. Liu, L., Persson, J. K. E., Svensson, M. & Aldskogius, H. (1998) Glial cell responses, complement and clusterin in the central nervous system following dorsal root transection. Glia 23, 221–238.Google Scholar
  27. Liu, L., Svensson., M. & Aldskogius, H. (1999) Glial cell responses and clusterin upregulation following rubrospinal tract lesion in the adult rat. Experimental Neurology 157, 69–76.Google Scholar
  28. May, P. C. & Finch, C. E. (1992) Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration. Trends in Neurosciences 15, 391–396.Google Scholar
  29. Mcdonald, J. F. & Nelsestuen, G. L. (1997) Potent inhibition of terminal complement assembly by clusterin: characterization of its impact on C9 polymerization. Biochemistry 36, 7464–7473.Google Scholar
  30. Morioka, T. & Streit, W. J. (1991) Expression of immunomolecules on microglial cells following neonatal sciatic nerve axotomy. Journal of Neuroimmunology 35, 21–30.Google Scholar
  31. Pasinetti, G. M., Johnson, S. A., Oda, T., Rozovsky, I. & Finch, C. E. (1994) Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain. Journal of Comparative Neurology 339, 387–400.Google Scholar
  32. Pasinetti, G. M., Tocco, G., Sakhi, S., Musleh, W. D., Desimoni, M. G., Mascarucci, P., Schreiber, S., Baudry, M. & Finch, C. E. (1996) Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicatenewroles for the C-system in neuronal and astrocytic functions. Neurobiology of Disease 3, 197–204.Google Scholar
  33. Persson, J. K. E., Svensson, M. & Aldskogius, H. (1995) Cell proliferation in the nucleus gracilis and dorsal spinal cord following sciatic nerve transection in the adult rat. Primary Sensory Neuron 1, 47–64.Google Scholar
  34. Reisert, I., Wildemann, G., Grab, D. & Pilgrim, C. H. (1984) The glial reaction in the course of axon regeneration: a stereological study of the hypoglossal nucleus. Journal of Comparative Neurology 229, 121–128.Google Scholar
  35. Robinson, A. P., White, T. M. & Mason, D. W. (1986) Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology 57, 239–247.Google Scholar
  36. Rosenberg, M. E. & Silkensen, J. (1995) Clusterin: physiologic and pathophysiologic considerations. International Journal of Biochemistry and Cell Biology 27, 633–645.Google Scholar
  37. Ruan, R. S., Leong, S. K. & Yeoh, K. H. (1995) The role of nitric oxide in facial motoneuronal death. Brain Research 698, 163–168.Google Scholar
  38. Scieszka, J. F., Maggiora, L. L., Wright, S. D. & Cho, M. J. (1991) Role of complements C3 and C5 in the phagocytosis of liposomes by human neutrophils. Pharmaceutical Research 8, 65–69.Google Scholar
  39. Sendtner, M., Holtmann, B. & Hughes, R. (1996) The response of motoneurons to neurotrophins. Neurochemical Research 21, 831–841.Google Scholar
  40. Smith, S. L., Oostveen, J. A. & Hall, E. D. (1996) Two novel pyrrolopyrimidine lipid peroxidation inhibitors U-101033E and U-104067F protect facial motor neurons following neonatal axotomy. Experimental Neurology 141, 304–309.Google Scholar
  41. Sprinkle, T. J. (1989) 2',3'-cyclic nucleotide 3'-phosphodiesterase, an oligodendrocyte-Schwann cell and myelin-associated enzyme of the nervous system. Critical Reviews in Neurobiology 4, 235–301.Google Scholar
  42. Streit, W. J. (1996) The role of microglia in brain injury. Neurotoxicology 17, 671–678.Google Scholar
  43. Sunderland, S. (1978) Regeneration of the axon and associated changes. In Nerves and Nerve Injuries, Ch. 8. Edinburgh: Churchill Livingstone.Google Scholar
  44. Svensson, M. & Aldskogius, H. (1992) Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury. Journal of Neuroimmunology 40, 99–110.Google Scholar
  45. Svensson, M., Eriksson, N. P. & Aldskogius, H. (1993) Evidence for activation of astrocytes via reactive microglial cells following hypoglossal nerve transection. Journal of Neuroscience Research 35, 373–381.Google Scholar
  46. Svensson, M., Mattsson, P. & Aldskogius, H. (1994) A bromodeoxyuridine labelling study of proliferating cells in the brainstem following hypoglossal nerve transection. Journal of Anatomy 185, 537–542.Google Scholar
  47. Svensson, M., Liu, L., Mattsson, P., Morgan, B. P. & Aldskogius, H. (1995) Evidence for activation of the terminal pathway of complement and upregulation of sulfated glycoprotein (SGP)-2 in the hypoglossal nucleus following peripheral nerve injury. Molecular and Chemical Neuropathology 24, 53–68.Google Scholar
  48. Torvik, A. (1972) Phagocytosis of nerve cells during retrograde degeneration. An electron microscopic study. Journal of Neuropathology and Experimental Neurology 31, 132–146.Google Scholar
  49. Vakeva, A., Laurila, P. & Meri, S. (1993) Codeposition of clusterin with the complement membrane attack complex in myocardial infarction. Immunology 80, 177–182.Google Scholar
  50. Villegas Perez, M. P., Vidal Sanz, M., Bray, G. M. & Aguayo, A. J. (1988) Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. Journal of Neuroscience 8, 265–280.Google Scholar
  51. Wu, W. & Li, L. (1993) Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neuroscience Letters 153, 121–124.Google Scholar
  52. Zwain, I. H., Grima, J. & Cheng, C. Y. (1994) Regulation of clusterin secretion and mRNA expression in astrocytes by cytokines. Molecular and Cellular Neuroscience 5, 229–237.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Ran Tao
    • 1
  • Håkan Aldskogius
    • 1
  1. 1.Department of NeuroscienceDivision of Neuroanatomy, Biomedical CenterUppsalaSweden

Personalised recommendations