Skip to main content
Log in

Use of a rat Y chromosome probe to determine the long-term survival of glial cells transplanted into areas of CNS demyelination

  • Published:
Journal of Neurocytology

Abstract

A lack of suitable markers for cells which undergo division following transplantation has hindered studies assessing the long-term survival of glial cell grafts in the CNS. A probe specific to the rat Y chromosome was used to identify male glial cells grafted into an area of ethidium bromide-induced demyelination in syngeneic adult female rat spinal cord 4 weeks, 6 months and 12 months post-transplantation. At all time points there was extensive oligodendrocyte remyelination of transplanted lesions, and graft-derived cells were present within the lesion up to 12 months post-transplantation. In order to demonstrate graft-derived oligodendrocytes in the remyelinated region at 6 and 12 months, double-labelling studies were performed using the oligodendrocyte-specific antibodies carbonic anhydrase II or phosphatidyl ethanolamine-binding protein in combination with the Y chromosome probe. It was found that the majority of oligodendrocytes in the transplanted region were graft-derived. Graft-mediated remyelination was associated with a reduction in myelin sheath thickness and increase in nodal frequency similar to that observed in spontaneous remyelination, suggesting that, like axons remyelinated spontaneously, axons remyelinated by grafted cells will be capable of secure conduction. An alteration in the immunoreactivity of oligodendrocytes from carbonic anhydrase II-negative in the unlesioned dorsal funiculus to carbonic anhydrase II-positive in the remyelinated dorsal funiculus was considered to reflect a reduction in the amount of myelin supported by each oligodendrocyte, leading to the proposal that carbonic anhydrase II immunoreactivity may provide a means of identifying areas of remyelination in normally carbonic anhydrase II-negative white matter tracts.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • ARENELLA, L. S. & HERNDON, R. M. (1984) Mature oligodendrocytes. Division following experimental demyelination in adult animals. Archives of Neurology 41, 1162–5.

    Google Scholar 

  • BAILEY, D. W. (1971) Allelic forms of a gene controlling the female immune response to the male antigen in mice. Transplantation 11, 426–8.

    Google Scholar 

  • BAILEY, D. W. & JOSTE, J. (1971) A gene governing the female immune response to the male antigen in mice. Transplantation 11, 404–7.

    Google Scholar 

  • BERNIER, I., TRESCA, J. P. & JOLLES, P. (1986) Ligandbinding studies with a 23 kDa protein purified from bovine brain cytosol. Biochimica et Biophysica Acta 871, 19–23.

    Google Scholar 

  • BILLINGHAM, R. E. & SILVERS, W. K. (1960) Studies on tolerance of the Y chromosome antigen in mice. Journal of Immunology 85, 14–16.

    Google Scholar 

  • BJARTMAR, C., HILDEBRAND, C. & LOINDER, K. (1994) Morphological heterogeneity of rat oligodendrocytes - electron microscope studies on serial sections. Glia 11, 235–44.

    Google Scholar 

  • BLAKEMORE, W. F. (1973) Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone. Journal of the Neurological Sciences 20, 73–83.

    Google Scholar 

  • BLAKEMORE, W. F. (1974a) Pattern of remyelination in the CNS. Nature 249, 577–8.

    Google Scholar 

  • BLAKEMORE, W. F. (1974b) Remyelination of the superior cerebellar peduncle in old mice following demyelination induced by cuprizone. Journal of the Neurological Sciences 22, 121–6.

    Google Scholar 

  • BLAKEMORE, W. F. (1976) Invasion of Schwann cells into the spinal cord of the rat following local injections of lysolethicin. Neuropathology and Applied Neurobiology 2, 21–39.

    Google Scholar 

  • BLAKEMORE, W. F. (1981) Observations on myelination and remyelination in the central nervous system. In Development in the Nervous System (edited by GARRAD, D. R. & FELDMAN, J. B.) pp. 289–308. Cambridge: Cambridge University Press.

    Google Scholar 

  • BLAKEMORE, W. F. (1982) Myelination, demyelination and remyelination in the CNS. In Recent Advances in Neuropathology, Volume 2 (edited by THOMAS-SMITH, W. & CAVANAGH, J. B.) pp. 53–82. Edinburgh: Churchill Livingstone.

    Google Scholar 

  • BLAKEMORE, W. F. & CRANG, A. J. (1988) Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system. Developmental Neuroscience 10, 1–11.

    Google Scholar 

  • BLAKEMORE, W. F. & CRANG, A. J. (1989) The relationship between type-1 astrocytes, Schwann cells and oligodendrocytes following transplantation of glial cell cultures into demyelinating lesions in the adult rat spinal cord. Journal of Neurocytology 18, 519–28.

    Google Scholar 

  • BLAKEMORE, W. F. & MURRAY, J. A. (1981) Qualitative examination of internodal length of remyelinated nervefibres in the central nervous system. Journal of the Neurological Sciences 49, 273–84.

    Google Scholar 

  • BLAKEMORE, W. F., CRANG, A. J., FRANKLIN, R. J. M., TANG, K. & RYDER, S. (1995) Glial cell transplants that are subsequently rejected can be used to influence regeneration of glial cell environments in the CNS. Glia 13, 79–91.

    Google Scholar 

  • BUTT, A. M., IBRAHIM, M., RUGE, F. M. & BERRY, M. (1995) Biochemical subtypes of oligodendrocyte in the anterior medullary velum of the rat as revealed by the monoclonal antibody Rip. Glia 14, 185–97.

    Google Scholar 

  • CAMMER, W. (1991) Immunostaining of carbamoylphosphate synthase II and fatty acid synthase in glial cells in rat, mouse, and hamster brains suggests roles for carbonic anhydrase in biosynthetic process. Neuroscience Letters 129, 247–50.

    Google Scholar 

  • DESQUENNE-CLARK, L. & CHEN, H.-D. (1987) Influence of the major histocompatibility complex (MHC) on the response to and expression of H-Y in rats. Developmental Genetics 8, 189–94.

    Google Scholar 

  • DUNCAN, I. D., HAMMANG, J. P., JACKSON, K. F., WOOD, P. M., BUNGE, R. P. & LANGFORD, L. (1988) Transplantation of oligodendrocytes and Schwann cells into the spinal cord of the myelin-deficient rat. Journal of Neurocytology 17, 351–60.

    Google Scholar 

  • ESSERS, J., DESTOPPELAAR, J. M. & HOEBEE, B. (1995) A new rat repetitive DNA family shows preferential localization on chromosome-3, chromosome-12 and chromosome y after fluorescence in situ hybridization and contains a subfamily which is Y-chromosome specific. Cytogenetics and Cell Genetics 69, 246–52.

    Google Scholar 

  • FRANKLIN, R. J. M., CRANG, A. J. & BLAKEMORE, W. F. (1991) Transplanted type-1 astrocytes facilitate repair of demyelinating lesions by host oligodendrocytes in adult rat spinal cord. Journal of Neurocytology 20, 420–30.

    Google Scholar 

  • GANSMULLER, A., LACHAPELLE, F., BARON-VAN EVERCOOREN, A., HAUW, J. J., BAUMANN, N. & GUMPEL, M. (1986) Transplantation of CNS fragments into the brain of shiverer newborn mice: extensive myelination by transplanted oligodendrocytes. II. Electron microscopic study. Developmental Neuroscience 8,197–207.

    Google Scholar 

  • GANSMULLER, A., CLERIN, E., KRUGER, F., GUMPEL, M. & LACHAPELLE, F. (1991) Tracing transplanted oligodendrocytes during migration and maturation in the shiverer mouse brain. Glia 4, 580–90.

    Google Scholar 

  • GASSER, D. L. & SILVERS, W. K. (1971) Genetic control of the immune response in mice. III An association between H-2 type and reaction to H-Y. Immunogenetics 15, 261–70.

    Google Scholar 

  • GLEDHILL, R. F. & MCDONALD, W. I. (1977) Morphological characteristics of central demyelination and remyelination - a single fibre study. Annals of Neurology 1, 552–60.

    Google Scholar 

  • GRAÇA, D. L. & BLAKEMORE, W. F. (1986) Delayed remyelination in rat spinal cord following ethidium bromide injection. Neuropathology and Applied Neurobiology 12,593–605.

    Google Scholar 

  • GUMPEL, M., BAUMANN, N., RAOUL, M. & JACQUE, C. (1983) Survival and differentiation of oligodendrocytes from neural tissue transplanted into new-born mouse brain. Neuroscience Letters 37, 307–11.

    Google Scholar 

  • HARVEY, A. R., FAN, Y., BEILHARZ, M. W. & GROUNDS, M. D. (1992) Survival and migration of transplanted male glia in adult female mouse brains monitored by a Y-chromosome-specific probe. Molecular Brain Research 12, 339–43.

    Google Scholar 

  • HARVEY, A. R., FAN, Y., CONNOR, A. M., GROUNDS, M. D. & BEILHARZ, M. W. (1993) The migration and intermixing of donor and host glia on nitrocellulose polymers implanted into cortical lesion cavities in adult mice and rats. International Journal of Developmental Neuroscience 11, 569–81.

    Google Scholar 

  • HILDEBRAND, C. & HAHN, R. (1978) Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species. Journal of the Neurological Sciences 38, 421–34.

    Google Scholar 

  • HILDEBRAND, C., REMAHL, S., PERSSON, H. & BJARTMAR, C. (1993) Myelinated nerve fibres in the CNS. Progress in Neurobiology 40, 319–84.

    Google Scholar 

  • KOMOLY, S., JEYASINGHAM, M. D., PRATT, O. E. & LANTOS, P. L. (1987) Decrease in oligodendrocyte carbonic-anhydrase activity preceding myelin degeneration in cuprizone induced demyelination Journal of the Neurological Sciences 79, 141–8.

    Google Scholar 

  • KORR, H., HORSMANN, C., SCHURMANN, M., DELAUNOY, J.-P. & LABOURDETTE, G. (1994) Problems encountered when immunocytochemistry is used for quantitative glial cell identification in autoradiographic studies of cell proliferation in the brain of the unlesioned adult mouse. Cell and Tissue Research 289, 85–95.

    Google Scholar 

  • LACHAPELLE, F., GUMPEL, M., BAULAC, M., JACQUE, C., DUC, P. & BAUMANN, N. (1983) Transplantation of CNS fragments into the brain of shiverer mutant mice: extensive myelination by implanted oligodendrocytes. Developmental Neuroscience 6, 325–34.

    Google Scholar 

  • LACHAPELLE, F., DUHAMEL-CLERIN, E., GANSMULLER, A., BARON-VAN EVERCOOREN, A., VILLAROYA, H. & GUMPEL, M. (1994) Transplanted transgenically marked oligodendrocytes survive, migrate and myelinate in the normal mouse brain as they do in the shiverer mouse brain. European Journal of Neuroscience 6, 814–24.

    Google Scholar 

  • LUDWIN, S. K. & MAITLAND, M. (1984) Long-term remyelination fails to reconstitute normal thickness of central myelin sheaths Journal of the Neurological Sciences 64,193–8.

    Google Scholar 

  • MATTHEWS, M. A. & DUNCAN, D. (1971) A quantitative study of morphological changes accompanying the initiation and progress of myelin production in the dorsal funicululs of the rat spinal cord. Journal of Comparative Neurology 142, 1–22.

    Google Scholar 

  • MORI, S. & LEBLOND, C. P. (1970) Electron microscopic study of the relationship between axon diameter and the initiation of myelin production in the peripheral nervous system. Anatomical Record 161, 337–51.

    Google Scholar 

  • MORRIS, C. S., ESIRI, M. M., SPRINKLE, T. J. & GREGSON, N. (1994) Oligodendrocyte reactions and cell proliferation markers in human demyelinating diseases. Neuropathology and Applied Neurobiology 20, 272–81.

    Google Scholar 

  • REMAHL, S. & HILDEBRAND, C. (1990) Relations between axons and oligodendroglial cells during initial myelination. I. The glial unit. Journal of Neurocytology 19, 313–28.

    Google Scholar 

  • ROSENBLUTH, J., HASEGAWA, M., SHIRASAKI, N., ROSEN, C. L. & LIU, Z. (1990) Myelin formation following transplantation of normal fetal glia into myelindeficient rat spinal cord. Journal of Neurocytology 19, 718–30.

    Google Scholar 

  • ROUSSEL, G., NUSSBAUM, F., SCHOENTGEN, F., JOLLES, P. & NUSSBAUM, J. L. (1988) Immunological investigation of a 21-kilodalton cytosolic basic protein in rat brain. Developmental Neuroscience 10, 65–74.

    Google Scholar 

  • SKOFF, R. P. & GHANDOUR, M. S. (1995) Oligodendrocytes in female carriers of the jimpy gene make more myelin than normal oligodendrocytes. Journal of Comparative Neurology 355, 124–33.

    Google Scholar 

  • SMITH, K. J., BLAKEMORE, W. F. & MCDONALD, W. I. (1979) Central remyelination restores secure conduction. Nature 280, 395–6.

    Google Scholar 

  • SMITH, K. J., BLAKEMORE, W. F. & MCDONALD, W. I. (1981) The restoration of conduction by central remyelination. Brain 104, 383–404.

    Google Scholar 

  • TANSEY, F. A., THAMPY, K. G. & CAMMER, W. (1988) Acetyl-CoA carboxylase in rat brain. II. Immunocytochemical localization. Developmental Brain Research 43,131–8.

    Google Scholar 

  • WACHTEL, S. S., GASSER, D. L. & SILVERS, W. K. (1973) Male specific antigen: modification of potency by the H-2 locus in mice. Science 181, 862–3.

    Google Scholar 

  • WOOD, P. M. & BUNGE, R. P. (1986) Evidence that axons are mitogenic for oligodendrocytes isolated from adult animals. Nature 320, 756–8.

    Google Scholar 

  • WOOD, P. M. & BUNGE, R. P. (1991) The origin of remyelinating cells in adult central nervous system: the role of the mature oligodendrocyte. Glia 4, 225–32.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'leary, M.T., Blakemore, W.F. Use of a rat Y chromosome probe to determine the long-term survival of glial cells transplanted into areas of CNS demyelination. J Neurocytol 26, 191–206 (1997). https://doi.org/10.1023/A:1018536130578

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018536130578

Keywords

Navigation