Galactosylsphingosine in Murine and Human Tissues of Normal and Globoid Cell Leukodystrophy Cases

  • Takuro Kobayashi
  • Hisaharu Shinoda
  • Ikuo Goto
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 150)


Globoid cell leukodystrophy (Krabbe’s disease, GLD) is a neurological dijogder of infancy caused by a genetic deficiency of galactosyl-ceramidase I.1,2 The murine analogue is twitcher mouse, in which galactosyl-ceramidase I is also deficient.3,4 The pathological features are similar to those of human GLD. In both, severe demyelination occurs in central and peripheral nervous tissues. In addition, gliosis, loss of oligodendrocytes, and presence of globoid cells are evident in the white matter. Galactosylceramide, a natural substrate of the deficient enzyme, apparently does not accumulate in the nervous tissues of human and murine cases of GLD. In 1972, Miyatake and Suzuki6 found that the hydrolysis of galactosylsphingosine (psychosine) is impaired in tissues from GLD patients and proposed, for the pathogenesis of GLD, the “psychosine hypothesis” which postulates that the degeneration of oligodendrocytes and consequent demyelination in the GLD tissue are due to the toxicity of galactosylsphingosine. In 1980, Svennerholm et al demonstrated an abnormal accumulation of galactosylsphingosine in the brains of GLD patients and supported the hypothesis. As to the twitcher mouse, Igisu and Suzuki8 noted an accumulation of the compound, determined by fluorometric assay using TLC. In this paper, we describe a procedure for the determination of galactosylsphingosine, using HPLC, and data on galactosylsphingosine content in tissues from normal and twitcher mice. The data on normal human tissues and tissues from a patient with GLD are also described.


Spinal Cord Sciatic Nerve Nervous Tissue Normal Human Tissue Twitcher Mouse 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    K. Suzuki, and Y. Suzuki, Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe’s disease), in: The Metabolic Basis of Inherited Disease, J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, eds., 5th edition, McGraw-Hill, New York, pp. 857 (1983).Google Scholar
  2. 2.
    T. Kobayashi, N. Shinnoh, I. Goto, and Y. Kuroiwa, Hydrolysis of galactosylceramide is catalyzed by two genetically distinct acid (3-galactosidases, J. Biol. Chem. 260:14892 (1985).Google Scholar
  3. 3.
    T. Kobayashi, T. Yamanaka, J. M. Jacobs, F. Teixeira, and K. Suzuki, The twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease), Brain Res. 202:479 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    T. Kobayashi, N. Shinnoh, and Y. Kuroiwa, Metabolism of galactosylceramide in the twitcher mouse, an animal model of human globoid cell leukodystrophy, Biochim. Biophys. Acta 879:215 (1986).Google Scholar
  5. 5.
    L. W. Duchen, E. M. Eicher, J. M. Jacobs, F. Scaravilli, and F. Teixeira, Hereditary leucodystrophy in the mouse. The new mutant twitcher, Brain 103:695 (1980).Google Scholar
  6. 6.
    T. Miyatake, and K. Suzuki, Globoid cell leukodystrophy: additional deficiency of psychosine galactosidase, Biochem. Biophys. Res. Commun. 48:538 (1972).CrossRefGoogle Scholar
  7. 7.
    L. Svennerholm, M.-T. Vanier, and J.-E. Mansson, Krabbe disease. A galactosylsphingosine (psychosine) lipidosis, J. Lipid Res. 21:53 (1980).Google Scholar
  8. 8.
    H. Igisu, and K. Suzuki, Progressive accumulation of toxic metabolite in a genetic leukodystrophy, Science 224:753 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    H. Shinoda, T. Kobayashi, M. Katayama, I. Goto, and H. Nagara, Accumulation of galactosylsphingosine (psychosine) in the twitcher mouse: Determination by HPLC, J. Neurochem. 49:92 (1987).Google Scholar
  10. 10.
    G. Rosenfelder, J.-Y. Chang, and D. G. Brown, Sphingosine determination at the picomole level using dimethylaminobenzene sulphonyl chloride, J. Chromatogr. 272:21 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    H. Igisu, and K. Suzuki, Analysis of galactosylsphingosine (psychosine in the brain, J. Lipid Res. 25:1000 (1984).PubMedGoogle Scholar
  12. 12.
    O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193:265 (1951).PubMedGoogle Scholar
  13. 13.
    T. Kobayashi, H. Nagara, K. Suzuki, and K. Suzuki, The twitcher mouse: determination of genetic status by galactosylceramidase assays on clipped tail, Biochem. Med. 27:8 (1982).Google Scholar
  14. 14.
    T. Kobayashi, H. Shinoda, I. Goto, T. Yamanaka, and Y. Suzuki, Globoid cell leukodystrophy is a generalized galactosylsphingosine (psychosine storage disease, Biochem. Biophys. Res. Commun. 144:41 (1987).Google Scholar
  15. 15.
    T. Taketomi, and K. Nishimura, Physiologic activity of psychosine, Jpn J. Exp. Med. 34:255 (1964).Google Scholar
  16. 16.
    L. H. Dickerman, T. W. Kurczynski, and R. G. Macbride, The effects of psychosine upon growth of human skin fibroblasts from patients with globoid cell leukodystrophy, J. Neurol. Sci. 50:181 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    O. Nilsson, J.-E. Mansson, G. Hakansson, and L. Svennerholm, Biochim. Biophys. Acta 712:453 (1982).PubMedGoogle Scholar
  18. 18.
    S. Neuenhofer, E. Conzelmann, G. Schwarzmgnn, H. Egge, and K. Sandhoff Occurrence of lysoganglioside lysoGM2 (II-Neu5Ac-gangliotriaosylsphingosine) in GM2 gangliosidosis brain, Biol. Chem. Hoppe-Seyler 367:241 (1986).Google Scholar
  19. 21.
    Y. A. Hannun, and R. M. Bell, Lysosphingolipids inhibit protein kinase C: Implication for the sphingolipidoses, Science 235:670 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    P. Strasberg, Cerebrosides and psychosine disrupt mitochondrial functions, Biochem. Cell Biol. 64:485 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    H. Igisu, and M. Nakamura, Inhibition of cytochrome c oxidase by psychosine (galactosylsphingosine), Biochem. Biophys. Res. Commun. 137:323 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Takuro Kobayashi
    • 1
  • Hisaharu Shinoda
    • 1
  • Ikuo Goto
    • 1
  1. 1.Department of Neurology, Neurological Institute Faculty of MedicineKyushu University 60Fukuoka 812Japan

Personalised recommendations