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Ultrastructure of the Gunn rat substantia nigra I. Cytoplasmic changes

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Summary

The substantia nigra of various aged hyperbilirubinemic (Gunn) rats was studied by means of electron microscopy. The cytological features observed in the neuronal somata were the presence of (1) complex membranous bodies (CMBs), (2) dilated cisternae of granular endoplasmic reticulum, (3) single membrane bound vacuoles and (4) enlarged mitochondria. Nearly every neuronal soma studied in two week old Gunn rats contained CMBs, which consisted of several layers of membrane that usually, but not always, surrounded small islands of cytoplasm. On occasion CMBs were seen to be directly connected with granular endoplasmic reticulum and, in a few instances, they were located within a cistern of endoplasmic reticulum. There were significantly fewer CMBs in the neuronal somata of adult Gunn rats. They were located peripherally in the somata or in the proximal portions of dendrites. Furthermore, in these animals the cytoplasm appeared normal and did not exhibit the features commonly seen in younger animals. Only a few hyperchromatic neurons were observed and no pronounced gliosis was evident. Therefore it is assumed that the majority of substantia nigra neurons recovered from the toxic effect of bilirubin or that the concentration of bilirubin deposited in the substantia nigra is not sufficient to be lethal. The hypothesis that is considered is that CMBs represent autophagic activity which results from exposure of neurons to bilirubin. The adjacent neurites and glia did not demonstrate the cytoplasmic changes that were characteristic of the neuronal somata.

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References

  • Aleu, F. P., Terry, R. D., Zellweger, H.: Electron microscopy of two cerebral biopsies in gargoylism. J. Neuropath. exp. Neurol.24, 304–317 (1965)

    Google Scholar 

  • Barron, K. D., Doolin, P. F., Oldershaw, J. B.: Ultrastructural observations on retrograde atrophy of lateral geniculate body. Neuronal Alteration J. Neuropath. exp. Neurol.26, 300–326 (1967)

    Google Scholar 

  • Barron, K. D., Means, E. D., Larsen, E.: Ultrastructure of retrograde degeneration in thalamus of rat. J. Neuropath. exp. Neurol.32, 218–244 (1973)

    Google Scholar 

  • Blanc, W. A., Johnson, L.: Studies on Kernicterus. Relationships with sulfonamide intoxication, report on kernicterus in rats with glucuronyl transferase deficiency and review of pathogenesis. J. Neuropath. exp. Neurol.18, 165–187 (1959)

    Google Scholar 

  • Blanc, W. A.: Kernicterus in Gunn's strain of rat. In: Kernicterus (ed. A. Sass-Korstak), pp. 150–152. Toronto: University of Toronto Press 1961

    Google Scholar 

  • Carbone, J. V., Grodsky, G. M.: Constitutional nonhemolytic hyperbilirubinemia in the rat: Defect of bilirubin conjugation. Proc. Soc. exp. Biol. (N. Y.)94, 461–463 (1957)

    Google Scholar 

  • Chen, H., Tsai, D., Wang, C., Chen, Y.: An electron microscopic and radioautographic study on experimental kernicterus. Amer. J. Path.56, 31–58 (1969)

    Google Scholar 

  • Claireaux, A. E., Cole, P. G., Lathe, G. H.: Icterus of the brain of the newborn. Lancet1953 II, 1226–1230

  • Colonnier, M.: Experimental degeneration in the cerebral cortex. Amer. J. Anat.98, 47–53 (1964)

    Google Scholar 

  • Cowger, M. L.: Mechanism of bilirubin toxicity on tissue culture cells: Factors that affect toxicity, reversibility by albumin, and comparison with other respiratory poisons and surfactants. Biochem. Med.5, 1016 (1971)

    Google Scholar 

  • Diamond, I., Schmid, R.: Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system. J. clin. Invest.45, 678–689 (1966)

    Google Scholar 

  • Ernster, L., Herlin, L., Zetterstrom, R.: Experimental studies of the pathogenesis of kernicterus. Pediatrics20, 647–652 (1957)

    Google Scholar 

  • Farrell, D. F., Baker, H. J., Herndon, R. M., Lindsey, J. R., McKhann, G. M.: Feline GM1 gangliosidosis: Biochemical and ultrastructural comparisions with the disease in man. J. Neuropath. exp. Neurol.32, 1 (1973)

    Google Scholar 

  • Fedorko, M. E., Hirsch, J. G., Cohn, Z. A.: Autophagic vacuoles produced in vitro. II. Studies on the mechanism of autophagic vacuoles produced by chloroquine. J. Cell Biol.38, 392–402 (1968)

    Google Scholar 

  • Gardner, W. A., Konigsmark, B. W.: Familial nonhemolytic jaundice: Bilirubinosis and encephalopathy. Pediatrics43, 365–376 (1969)

    Google Scholar 

  • Gunn, C. K.: Hereditary acholuric jaundice in the rat. Canad. med. Ass. J.50, 230–237 (1944)

    Google Scholar 

  • Hruban, Z., Spargo, B., Swift, H., Wissler, R. W., Kleinfeld, R. G.: Focal cytoplasmic degradation. Amer. J. Path.42, 657–683 (1963)

    Google Scholar 

  • Hwang, K. M., Yang, L. C., Carrico, C. K., Schulz, R. A., Schenkman, J. B., Sartorelli, A. C.: Production of membrane whorls in ra liver by some inhibitors of protein synthesis. J. Cell Biol.62, 20–31 (1974)

    Google Scholar 

  • Johnson, L.: The effects of certain substances on bilirubinic levels and the occurrence of kernicterus in generally jaundiced rats. In: Kernicterus (ed. A. Sass-Korstak), pp. 208–218. Toronto: University of Toronto Press 1961

    Google Scholar 

  • Johnson, L., Garcia, M. L., Figueroa, E., Sarmiento, F.: Kernicterus in rats lacking glucuronyl transferase. Am. J. Dis. Child.101, 322–349 (1961)

    Google Scholar 

  • Kirkpatrick, J. B.: Chromatolysis in the hypoglossal nucleus of the rat: An electron microscopic analysis. J. comp. Neurol.132, 189–212 (1968)

    Google Scholar 

  • Lehninger, A. L.: Water uptake and extrusion by mitochondria in relation to oxidative phosphorylation. Physiol. Rev.42, 467–517 (1962)

    Google Scholar 

  • Lehninger, A. L.: In: The Mitochondrion, molecular basis of structure and function. New York: W. A. Benjamin 1964

    Google Scholar 

  • Lüllmann-Rauch, R.: Lipodosis-like alterations in hypothalamic neurosecretory cells of rats treated with chlorphentermine or iprindole. Cell Tiss. Res.149, 587–590 (1974)

    Google Scholar 

  • Lüllmann-Rauch, R., Reil, G. H., Rossen, E., Seiler, K. U.: The ultrastructure of rat lung changes induced by an anorganic drug (chlorphentermine). Virchows Arch., Abt. B, Zellpath.11, 167–181 (1972)

    Google Scholar 

  • Lüllmann-Rauch, R., Pietschmann, N.: Lipodosis-like cellular alterations in lymphatic tissues of chlorphentermine-treated animals. Virchows Arch., Abt. B, Zellpath.15, 295–308 (1974)

    Google Scholar 

  • Matthews, M. A.: Death of the central neuron: an electron microscopic study of thalamic retrograde degeneration following cortical ablation. J. Neurocytol.2, 265–288 (1973)

    Google Scholar 

  • Novikoff, A. B.: Lysosomes in nerve cells. In: The neuron (ed. H. Hyden), pp. 255–377. Amsterdam-London-New York: Elsevier Publ. Co. 1967

    Google Scholar 

  • Odell, G. B.: Factors influencing the binding of bilirubin by albumin in kernicterus. In: Kernicterus (ed. A. Sass-Korstak), pp. 199–207. Toronto: University of Toronto Press 1961

    Google Scholar 

  • Reynolds, E. S.: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell Biol.17, 208–212 (1963)

    Google Scholar 

  • Samuels, S., Gonatas, N. K., Weiss, M.: Formation of membranous cytoplasmic bodies in Tay-Sachs disease: An in vitro study. J. Neuropath. exp. Neurol.24, 256–264 (1965)

    Google Scholar 

  • Schmid, R., Axelrod, J., Hammaker, L., Swarm, R. L.: Congenital jaundice in rats, due to a defect in glucuronide formation. J. clin. Invest.37, 1123–1130 (1958)

    Google Scholar 

  • Schutta, H. S., Johnson, L.: Bilirubin encephalopathy in the Gunn rat: A fine structural study of the cerebellar cortex. J. Neuropath. exp. Neurol.26, 377–396 (1967)

    Google Scholar 

  • Schelburne, J. D., Arstila, A. U., Trump, B. F.: Studies on cellular autophagocytosis, cyclic AMP and dibutyryl cyclic AMP stimulated autophagy in rats. Amer. J. Path.72, 521–540 (1973)

    Google Scholar 

  • Silberberg, D. H., Schutta, H. S.: The effects of unconjugated bilirubin and related pigments on cultures of rat cerebellum. J. Neuropath. exp. Neurol.26, 572–583 (1967)

    Google Scholar 

  • Stern, J., Novikoff, A. B., Terry, R. D.: The induction of sulfatide, ganglioside, and cerebroside storage in organized nervous system cultures. In: Sphingolipids, Sphinglolipidoses, and allied disorders (eds. B. W. Volk and S. M. Aronson), pp. 651–660. New York: Plenum Press 1972

    Google Scholar 

  • Tapley, D. F., Cooper, G.: Effect of thyroxine on the swelling of mitochondria isolated from various tissues of the rat. Nature (Lond.)167, 1119 (1956)

    Google Scholar 

  • Terry, R. D., Weiss, M.: Studies in Tay-Sachs disease. II. Ultrastructure of the cerebrum. J. Neuropath. exp. Neurol.22, 18–55 (1963)

    Google Scholar 

  • Trump, B. F., Croker, B. P., Mergener, W. J.: The role of energy metabolism, ion, and water shifts in the pathogenesis of cell injury. In: Cell membranes, biological and pathological aspects (eds. G. W. Richter, D. G. Scarpelli), pp. 84–128. Baltimore: The Williams and Wilkins Co. 1971

    Google Scholar 

  • Waters, W. J., Richert, D. A., Rawson, H. H.: Bilirubin encephalopathy. Pediatrics13, 319–325 (1954)

    Google Scholar 

  • Waters, W. J., Britton, H. A.: Bilirubin encephalopathy: Preliminary studies related to production. Pediatrics15, 45–48 (1955)

    Google Scholar 

  • Wuerker, R. B., Palay, S. L.: Neurofilaments and microtubules in anterior horn cells of the rat. Tissue and Cell1, 387–402 (1969)

    Google Scholar 

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Batty, H.K., Millhouse, O.E. Ultrastructure of the Gunn rat substantia nigra I. Cytoplasmic changes. Acta Neuropathol 35, 93–107 (1976). https://doi.org/10.1007/BF00690556

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