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Immunocytochemical localization of d-amino acid oxidase in rat brain

  • Published:
Journal of Neurocytology

Abstract

d-amino acid oxidase (d-AAO) is a peroxisomal flavoenzyme, the physiological substrate and the precise function of which are still unclear. We have investigated D-AAO distribution in rat brain, by immunocytochemistry, with an affinity-purified polyclonal antibody. Immunoreactivity occurred in both neuronal and glial cells, albeit at different densities. Glial immunostaning was strongest in the caudal brainstem and cerebellar cortex, particularly in astrocytes, Golgi-Bergmann glia, and tanycytes. Hindbrain neurons were generally more immunoreactive than those in the forebrain. Immunopositive forebrain cell populations included mitral cells in the olfactory bulb, cortical and hippocampal neurons, ventral pallidum, and septal, reticular thalamic, and paraventricular hypothalamic nuclei. Within the positive regions, not all the neuronal populations were equally immunoreactive; for example, in the thalamus, only the reticular and anterodorsal nuclei showed intense labelling. In the hindbrain, immunopositivity was virtually ubiquitous, and was especially strong in the reticular formation, pontine, ventral and dorsal cochlear, vestibular, cranial motor nuclei, deep cerebellar nuclei, and the cerebellar cortex, especially in Golgi and Purkinje cells.

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References

  • Adams, J. C. (1992) Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains. Journal of Histochemistry and Cytochemistry 40, 1457–1463.

    Google Scholar 

  • Angermuller, S. (1989) Peroxisomal oxidases: cytochemical localization and biological relevance. Progress in Histochemistry and Cytochemistry 20, 1–63.

    Google Scholar 

  • Arnold, G., Liscum, L. & Holtzman, E. (1979) Ultrastructural localization of D-amino acid oxidase in microperoxisomes in the rat nervous system. Journal of Histochemistry and Cytochemistry 27, 735–745.

    Google Scholar 

  • Beard, M. E., Davies, T., Holloway, M. & Holtzman, E. (1988) Peroxisomes in pigment epithelium and Muller cells of amphibian retina possess Damino acid oxidase as well as catalase. Experimental Eye Research 47, 795–806.

    Google Scholar 

  • Bright, H. J. & Porter, D. J. T. (1975) Flavoprotein oxidases. In The Enzymes, Vol. 12: (edited by Boyer, P. D.), pp. 421–505. New York: Academic Press.

    Google Scholar 

  • Cimini, A. M., Moreno, S., Serafini, B. & Cerù, M. P. (1993) Purification of peroxisomal fraction from rat brain. Neurochemistry International 23, 249–260.

    Google Scholar 

  • Cimini, A. M., Singh, I., Farioli vecchioli, S., Cristiano, L. & Cerù, M. P. (1998) Presence of heterogeneous peroxisomal populations in the rat nervous tissue. Biochimica et Biophysica Acta 1425, 13–26.

    Google Scholar 

  • Dõaniello, A., Dõonofrio, G., Peschetola, M., Dõaniello, G., Vetere, A., Petrucelli, L. & Fischer, G. H. (1993) Biological role of D-amino acid oxidase and D-aspartate oxidase: effects of D-amino acids. Journal of Biological Chemistry 268, 26941–26949.

    Google Scholar 

  • Dõaniello, A., Vetere, A. & Petrucelli, L. (1993a) Further study on the specificity of D-amino acid oxidase and of D-aspartate oxidase and time course for complete oxidation of D-amino acids. Comparative Biochemistry and Physiology 105 B, 731–734.

    Google Scholar 

  • Dixon, M. & Kleppe, K. (1965) D-amino acid oxidase: II. Specificity, competitive inhibition and reaction sequence. Biochimica et Biophysica Acta 96, 368–382.

    Google Scholar 

  • Fedele, E., Bisaglia, M. & Raiteri, M. (1997) D-serine modulates the NMDA receptor/nitric oxide/cGMP pathway in the rat cerebellum during in vivo microdialysis. Naunyn-SchmiedebergÕs Archives Pharmacology 355, 43–47.

    Google Scholar 

  • Fitzpatrick, P. F. & Massey, V. (1982) Thiazolidine-2-carboxylic acid, an adduct of cysteamine and glyoxilate, as a substrate for D-amino acid oxidase. Journal of Biological Chemistry 257, 1166–1171.

    Google Scholar 

  • Gaunt, G. L. & De Duve, C. (1976) Subcellular distribution of D-amino acid oxidase and catalase in rat brain. Journal of Neurochemistry 26, 749–759.

    Google Scholar 

  • Hamilton, G. A. (1985) Peroxisomal oxidases and suggestions for the mechanism of action of insulin and other hormones. Advances in Enzymology 57, 85–178.

    Google Scholar 

  • Hashimoto, A., Nishikawa, T., Hayashi, T., Fuji, N., Harada, K., Oka, T. & Takahashi, K. (1992) The presence of free D-serine in rat brain. FEBS Letters 296, 33–36.

    Google Scholar 

  • Hashimoto, A., Nishikawa, T., Oka, T. & Takahashi, K. (1993) Endogenous D-serine in rat brain: N-methyl-D-aspartate receptor-related distribution and aging. Journal of Neurochemistry 60, 783–786.

    Google Scholar 

  • Hashimoto, A., Oka, T. & Nishikawa, T. (1995) Anatomical distribution and post-natal changes in endogenous free D-aspartate and D-serine in rat brain and periphery. European Journal of Neuroscience 7, 1657–1663.

    Google Scholar 

  • Holtzman, E. (1982) Peroxisomes in nervous tissue. Annals of the New York Academy of Sciences 386, 523–525.

    Google Scholar 

  • Horiike, K., Arai, R., Tojo, H., Yamano, T., Nozaki, M. & Maeda, T. (1985) Histochemical staining of cells containing flavoenzymeD-amino acid oxidase based on its enzymatic activity: application of a coupled peroxidation method. Acta Histochemica et Cytochemica 18, 539–550.

    Google Scholar 

  • Horiike, K., Tojo, H., Arai, R., Yamano, T., Nozaki, M. & Maeda, T. (1987) Localization of Damino acid oxidase in Bergmann glial cells and astrocytes of rat cerebellum. Brain Research Bullettin 19, 587–596.

    Google Scholar 

  • Horiike, K., Tojo, H., Arai, R., Nozaki, M. & Maeda, T. (1994) D-Aminoacid oxidase is confined to the lower brain stem and cerebellum in rat brain: regional differentiation of astrocytes. Brain Research 652, 297–303.

    Google Scholar 

  • Jules, R. S., Kennard, J., Setlik, W. & Holtzman, E. (1991) Peroxisomal oxidation of thiazolidine carboxylates in firefly fat body, frog retina, and rat liver and kidney. European Journal of Cell Biology 55, 94–103.

    Google Scholar 

  • Konno, R., Sasaki, M., Asakura, S., Fukui, K., Enami, J. & Niwa, A. (1997) D-Amino-acid oxidase is not present in the mouse liver. Biochimica et Biophysica Acta 1335, 173–181.

    Google Scholar 

  • Konno, R., Uchyama, S. & Yasumura, Y. (1982) Intraspecies and interspecies variations in the substrate specificity of D-amino acid oxidase. Comparative Biochemistry and Physiology 71B, 735–738.

    Google Scholar 

  • Konno, R. & Yasumura, Y. (1983) Mouse mutant deficient in D-aminoacid oxidase activity. Genetica 103, 277–284.

    Google Scholar 

  • Konno, R. & Yasumura, Y. (1992) D-amino-acid oxidase and its physiological function. International Journal of Biochemistry 24, 519–524.

    Google Scholar 

  • Krebs, H. A. (1935) Metabolism of amino-acids. III. Deamination of amino-acids. Biochemical Journal 29, 1620–1644.

    Google Scholar 

  • Laemmli, E. K. (1970) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227, 680–685.

    Google Scholar 

  • Mannaerts, G. P. & Van Veldhoven, P. P. (1993) Metabolic role ofmammalianperoxisome. In Peroxisomes. Biology and Importance in Toxicology and Medicine (edited by Gibson, G. & Lake, B.), pp. 19–62. London: Taylor & Francis.

    Google Scholar 

  • Masters, C. (1997) Gluconeogenesis and the peroxisome. Molecular and Cellular Biochemistry 166, 159–168.

    Google Scholar 

  • Moreno, S., Mugnaini, E. & Cerù, M. P. (1995) Immunocytochemical localization of catalase in the central nervous system of the rat. Journal of Histochemistry and Cytochemistry 43, 1253–1267.

    Google Scholar 

  • Moreno, S., Nardacci, R. & Cerù, M. P. (1997) Regional and ultrastructural immunolocalization of copper-zinc superoxide dismutase in rat central nervous system. Journal of Histochemistry and Cytochemistry 45, 1611–1622.

    Google Scholar 

  • Moser, H. W. (1987) New approaches in peroxisomal disorders. Developmental Neuroscience 9, 1–18.

    Google Scholar 

  • Mugnaini, E. & Dahl, A. L. (1983) Zinc-aldehyde fixation for light microscopic immunocytochemistry of nervous tissues. Journal of Histochemistry and Cytochemistry 31, 1435.

    Google Scholar 

  • Mugnaini, E. & Oertel, W. H. (1985) An atlas of the distribution GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In Handbook of Chemical Neuroanatomy (edited by Bjorklund, A. & Hokfelt, T.) Vol. 4. Part I: pp. 436–608. New York: Elsevier.

    Google Scholar 

  • Nagata, Y. (1992) Involvement of D-amino acid oxidase in elimination of D-serine in mouse brain. Experientia 48, 753–755.

    Google Scholar 

  • Nagata, Y., Horiike, K. & Maeda, T. (1994) Distribution of free D-serine in vertebrate brains. Brain Research 634, 291–295.

    Google Scholar 

  • Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates, 2nd ed. San Diego: Academic Press.

    Google Scholar 

  • Perotti, M.E., Gavazzi, E., Trussrdo, L., Malgaretti, N. & Curti, B. (1987) Immunoelectron microscopic localization of D-amino acid oxidase in rat kidney and liver. Histochemical Journal 19, 157–169.

    Google Scholar 

  • Ronchi, S., Minchiotti, L., Galliano, M., Curti, B., Swenson, R. P., Williams, C. H. & massey, V. (1982) The primary structure of D-amino acid oxidase from pig kidney. Journal of Biological Chemistry 257, 8824–8834.

    Google Scholar 

  • Schell, M. J., Molliver, M. E. & Snyder, S. H. (1995) D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. Proceedings of the National Academy of Sciences USA 92, 3948–3952.

    Google Scholar 

  • Towbin, H., Stahelin, T. & Gordon., J. (1979) Electrophoretic transfer of proteins frompolyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences USA 76, 4350–4354.

    Google Scholar 

  • Usuda, N., Yokota, S., Hashimoto, T. & Nagata, T. (1986) Immunocytochemical localization of D-amino acid oxidase in the central clear matrix of rat kidney peroxisomes. Journal of Histochemistry and Cytochemistry 34, 1709–1718.

    Google Scholar 

  • Usuda, N., Yokota, S., Ichikawa, R., Hashimoto, T. & Nagata, T. (1991) Immunoelectron microscopic study of a new D-aminoacid oxidase-immunoreactive subcompartment in rat liver peroxisomes. Journal of Histochemistry and Cytochemistry 39, 95–102.

    Google Scholar 

  • Van Den Bosch, H., Schutgens, R. B. H., Wanders, R. J. A. & Tager, J. M. (1992) Biochemistry of peroxisomes. Annual Reviews in Biochemistry 61, 157–197.

    Google Scholar 

  • Van Roermund, C. W. T., Van Den Berg, M. & Wanders, R. J. A. (1995) Localization of 3-oxoacyl-CoA thiolase in particles of varied density in rat liver: implications for peroxisome biogenesis. Biochimica et Biophysica Acta 1245, 348–358.

    Google Scholar 

  • Weimar, W. R. & Neims, A. H. (1977) Hog cerebellar D-amino acid oxidase and its histochemical and immunofluorescence localization. Journal of Neurochemistry 28, 559–572.

    Google Scholar 

  • Zaar, K. (1992) Structure and function of peroxisomes in the mammalian kidney. European Journal of Cell Biology 59, 233–254.

    Google Scholar 

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Moreno, S., Nardacci, R., Cimini, A. et al. Immunocytochemical localization of d-amino acid oxidase in rat brain. J Neurocytol 28, 169–185 (1999). https://doi.org/10.1023/A:1007064504007

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