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Accumulation of sulfatide in neuronal and glial cells of arylsulfatase A deficient mice

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Journal of Neurocytology

Abstract

Arylsulfatase A (ASA) degrades sulfatide, seminolipid and lactosylceramide sulfate, glycolipids recognized by the Sulph I antibody although sulfatide is considered the main antigen. Sulfatide is myelin associated but studies have shown a minor distribution also in non-myelin forming cells. The aim of this work was to further study sulfatide in neurons and astrocytes by immunohistochemistry, facilitated by investigation of tissue from adult ASA deficient (ASA −/−) mice. Cells with a low presence of sulfatide might be detected due to lack of ASA activity and accumulation of Sulph I antigens. Sulfatide positive astrocytes and neurons were more numerous and intensely stained in ASA −/− mice, demonstrating a sulfatide accumulation compared to controls. Sulph I staining was especially increased in the molecular layer of cerebellum, in which Purkinje cell dendrites displayed an altered morphology, and in layer IV–VI of cerebral cortex. In hippocampus, immunostaining was found in neuronal cytoplasm in ASA −/− but in nuclear membranes of control mice. We observed a gray matter astrogliosis, which appeared to be associated to sulfatide accumulation. In addition, the developmental change (<20 months) of Sulph I antigens, galactosylceramide, phospholipids and cholesterol were followed by lipid analyses which verified sulfatide and seminolipid accumulation in adult ASA −/− mice, although no lactosylceramide sulfate could be detected. In addition to demonstrating sulfatide in neurons and astrocytes, this study supports the value of ASA −/− mice as a model for metachromatic leukodystrophy and suggests that accumulation of sulfatide beyond myelin might contribute to the pathology of this disease.

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References

  • Abe, T. & Norton, W. T. (1974) The characterization of sphingolipids from neurons and astroglia of im-mature rat brain. Journal of Neurochemistry 23, 1025–1036.

    Google Scholar 

  • Baumann, N., Turpin, J. C., Lefevre, M. & Colsch, B. (2002) Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships ? Journal of Physiology 96, 310–306.

    Google Scholar 

  • Berntson, Z., Hansson, E., RÖNNBÄCK, L. & Fredman, P. (1998) Intracellular sulfatide expression in a subpopulation of astrocytes in primary cultures. Journal of Neuroscience Research 52, 559–568.

    Google Scholar 

  • Betts, T. A., Smith, W. T. & Kelly, R. E. (1968) Adult metachromatic leukodystrophy (sulphatide lipidosis) simulating acute schizophrenia. Neurology 18, 1140–1142.

    Google Scholar 

  • Burkart, T., Caimi, L., Herschkowitz, N. N. & Wiesmann, U. N. (1983) Metabolism of sulfogalactosyl glycerolipids in the myelinating mouse brain. Developmental Biology 98, 182–186.

    Google Scholar 

  • COnsiglio, A., Quattrini, A., Martino, S., Bensadoun, J.C., Dolcetta, D., Trojani, A., Benaglia, G., Marchesini, S., Cestari, V., Oliverio, A., Bordignon, C. & Naldini, L. (2001) In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: Correction of neuropathology and protection against learning impairments in affected mice. Nature Medicine 7, 310–316.

    Google Scholar 

  • Crawford, N. (1958) An improved method for the de-termination of free and total cholesterol using the ferric chloride reaction. Clinica Chimica Acta 3, 357–367.

    Google Scholar 

  • Fredman, P., Mattsson, L., Andersson, K., Davidsson, P., Ishizuka, I., Jeansson, S., Mansson, J.-E. & Svennerholm, L. (1988) Characterization of the binding epitope of a monoclonal antibody to sulphatide. Biochemical Journal 251,17-22.

    Google Scholar 

  • Fredman, P., Mansson, J.-E., Bigner, S. H., Wikstrand, C. J., Bigner, D. D. & Svennerholm, L. (1990) Gangliosides in the human glioma cell line U-118 MG grown in culture or as xenografs in nude rats. Biochimica et Biophysica Acta 1045, 239–244.

    Google Scholar 

  • Fredman, P., Mansson, J.-E., Rynmark, B.-M., Josefsen, K., Ekblond, A., Halldner, L., Osterbye, T., Horn, T. & Buschard, K. (2000) The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: Possible involvement in insulin trafficking. Glycobiology 10,39–50.

    Google Scholar 

  • Ghardashkhani, S., Gustavsson, M. L., Breimer, M. E., Larsson, G. & Samuelsson, B. E. (1995) Negative electrospray ionization mass spectrometry analysis of gangliosides, sulfatides and cholesterol 3-sulfate. Rapid Communications in Mass Spectrometry 9, 491–494.

    Google Scholar 

  • Godfraind, C., Friedrich, V. L., Holmes, K. V. & Dubois-Dalcq, M. (1989) In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice. Journal of Cell Biology 109, 2405–2416.

    Google Scholar 

  • Goebel, H. H., Argyrakis, A., Shimokawa, K., Seidel, D. & Heipertz, R. (1980) Adult Metachromatic Leukodystrophy, IV. Ultrastructural studies on the central and peripheral nervous system. European Neurology 19, 294–307.

    Google Scholar 

  • Guseo, A., Deak, G. & Szirmai, I. (1975) An adult case of metachromatic leukodystrophy. Light, polarization and electron microscopic study. Acta Neuropathology 32, 333–339.

    Google Scholar 

  • Han, X., Cheng, H., Fryer, J. D., Fagan, A. M. & Holtzman, D. M. (2003) Novel role for apolipoprotein E in the central nervous system. Modulation of sulfatide content. Journal of Biological Chemistry 278, 8043–8051.

    Google Scholar 

  • Hess, B., Saftig, P., Hartmann, D., Coenen, R., LÜullmann-Rauch, R., Goebel, H. H., Evers, M., Von Figura, K., D'Hooge, R., Nagels, G., De Deyn, P., Peters, C. &Gieselmann, V. (1996) Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy. Proceedings of the National Academy of Sciences of the USA 93, 14821–14826.

  • D'Hooge, R., Hartmann, D., Manil, J., Colin, F., Gieselmann, V. & De Deyn, P. P. (1999) Neuromotor alterations and cerebellar deficits in aged arylsulfatase A-deficient mice. Neuroscience Letters 273,93–96.

    Google Scholar 

  • Iida, N., Toida, T., Kushi, Y., Handa, S., Fredman, P., Svennerholm, L. & Ishizuka, I. (1989) A sulfated glucosylceramide from rat kidney. Journal of Biological Chemistry 264, 5974–5980.

    Google Scholar 

  • Ishizuka, I., Inomata, M., Ueno, K. & YAmakawa, T. (1978) Sulfated glyceroglycolipids in rat brain. Journal of Biological Chemistry 253, 898–907.

    Google Scholar 

  • Ishizuka, I. & Inomata, M. (1979) Sulfated glycoglycerolipids in rat brain: Decrease and disappearance af-ter developmental age. Journal of Neurochemistry 33, 387–388.

    Google Scholar 

  • Ishizuka, I. (1997) Chemistry and functional distribution of sulfoglycolipids. Progress in Lipid Research 36, 245–319.

    Google Scholar 

  • Janeczko, K. (1993) Co-expression of GFAP and vimentin in astrocytes proliferating in respond to injury in the mouse hemisphere. A combined autoradiographic and double immunohistochemical study. International Journal of Developmental Neuroscience 11, 139–147.

    Google Scholar 

  • Lampert, I. A. & Lewis, P. D. (1975) Staining of sulfatides in metachromatic leukodystrophy with alcian Blue at high salt concentrations. Histochemistry 43, 269–273.

    Google Scholar 

  • Levine, M., Kornblatt, M. J. & Murray, R. K. (1975) Isolation and partial characterization of a sulfogalactoglycerolipid from rat brain. Canadian Journal of Biochemistry 53, 679–689.

    Google Scholar 

  • Neter, J., Kutner, M. H., Nachtsheim, C. J. & Wasserman, W. (1996) Qualitative predictor variables. In Applied Linear Regression Models (edited by Neter J., Kutner, M. H., Nachtsheim C. J. & Wasserman W) pp. 461–464. Chicago, Irwin.

    Google Scholar 

  • Nonaka, G. & Kishimoto, Y. (1979) Levels of cerebrosides, sulfatides, and galactosyl diglycerides in different regions of rat brain. Change during maturation and distribution in subcellular fractions of gray and white matter of sheep brain. Biochimica et Biophysica Acta 572, 432–441.

    Google Scholar 

  • Norton, W. T & Autilio, L. A. (1966) The lipid composition of purified bovine brain myelin. Journal of Neurochemistry 13, 213–222.

    Google Scholar 

  • Norton, W. T. & Cammer, W.(1984) Isolation and characterization of myelin. In Myelin (edited by Morell P.) pp. 147–180. New York: Plenum Press.

    Google Scholar 

  • Peng, L. & Suzuki, K. (1987) Ultrastructural study of neurons in metachromatic leukodystrophy. Clinical Neuropathology 6, 224–230.

    Google Scholar 

  • Pernber, Z., Molander-Melin, M., Berthold, C.-H., Hansson, E. & Fredman, P. (2002) Expression of the myelin and oligodendrocyte progenitor marker--sulfatide--in neurons and astrocytes of adult rat brain. Journal of Neuroscience Research 69,86–93.

    Google Scholar 

  • Rosengren, B., Fredman, P., Mansson, J.-E. & Svennerholm, L. (1989) Lysosulfatide (galactosylsphingosine-3-O-sulfate) from metachromatic leukodystrophy and normal human brain. Journal of Neurochemistry 52, 1035–1041.

    Google Scholar 

  • Sourander, P. & Svennerholm, L. (1962) Sulphatide lipidosis in the adult with the clinical picture.Neuronal accumulation of sulfatide 427 of progressive organic dementia with epileptic seizures. Acta Neuropathologica 1, 384–396.

    Google Scholar 

  • Svennerholm, L. & Vanier, M. T. (1972) The distribution of lipids in the human nervous system. II. Lipid composition of human fetal and infant brain. Brain Research 47, 457–468.

    Google Scholar 

  • Svennerholm, L. & Fredman, P. (1980) A procedure for the quantitative isolation of brain gangliosides. Biochimica et Biophysica Acta 617,97–109.

    Google Scholar 

  • Svennerholm, L., Fredman, P., Jungbjer, B., Mansson, J.-E., Rynmark, B.-M., Boström, K., Hagberg, B., Noren, L. & Santavuori, S. (1987) Large alterations in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis. Journal of Neurochemistry 49, 1772–1783.

    Google Scholar 

  • Svennerholm, L., Boström, K., Fredman, P., Mansson, J.-E. & Rynmark, B.-M. (1992) Membrane lipids of human perioheral nerve and spinal cord. Biochimica et Biophysica Acta 1128,1–7.

  • Takamiya, Y., Kohsaka, S., Toya, S., Otani, M. & Tsukada, Y. (1988) Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats. Developmental Brain Research 38, 201–210.

    Google Scholar 

  • Von Figura, K., Gieselmann, V. & Jaeken, J. (2001) Metachromatic leukodystrophy: Lysosomal disorders. In The Metabolic and Molecular Bases of Inherited Disease. (edited by Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) pp. 3695–3724. New York: McGraw-Hill.

    Google Scholar 

  • Yamano, T., Ohta, S., Shimada, M., Okada, S., Yutaka, T., Sugita, T. & Yabuuchi, H. (1980) Neuronal depletion of cerebellum in late infantile metachromatic leukodystrophy. Brain and Development 2, 359–364.

  • Zalc, B., Monge, M., Dupouey, P., Hauw, J. J. & Baumann, N. A. (1981) Immunohistochemical localization of galactosyl and sulfogalactosyl ceramide in the brain of the 30-day-old mouse. Brain Research 211, 341–354.

    Google Scholar 

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Authors and Affiliations

  1. Institite of Clinical Neuroscience, Experimental Neuroscience Section,The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, SE-431 80, Mölndal, Sweden

    Marie Molander-Melin, Zarah Pernber, Jan-Eric Månsson & Pam Fredman

  2. Institut fur Physiologische Chemie, Universität Bonn, Nussallee 11, D-53 115, Bonn, Germany

    Sebastian Franken & Volkmar Gieselmann

Authors
  1. Marie Molander-Melin
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  2. Zarah Pernber
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  3. Sebastian Franken
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  4. Volkmar Gieselmann
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  5. Jan-Eric Månsson
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  6. Pam Fredman
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Molander-Melin, M., Pernber, Z., Franken, S. et al. Accumulation of sulfatide in neuronal and glial cells of arylsulfatase A deficient mice. J Neurocytol 33, 417–427 (2004). https://doi.org/10.1023/B:NEUR.0000046572.53905.2c

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