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Acta Neuropathologica

, Volume 9, Issue 2, pp 146–157 | Cite as

Histological studies on the effect of actinomycin D on retrograde nerve cell reaction in the facial nucleus of mice

  • Ansgar Torvik
  • Anna Heding
Original Investigations

Summary

The retrograde reaction in the facial nucleus of mice has been studied after intracerebral injection of actinomycin D. Normally these neurons show increasing cytoplasmic basophilia and decreasing size of the Nissl granules during the first days after section of the facial nerve. The nerve cell diameter increases between the 2nd and 4th day after section of the nerve.

After intracerebral injection of actinomycin D the nucleolus of all neurons disintegrates rapidly while the cytoplasm shows only slight changes. The Nissl substance of normal neurons appears well preserved after 2 days' treatment.

When actinomycin is given at the time of section of the facial nerve, all aspects of retrograde reaction is blocked during the next 48 hours. The findings suggest that the dispersion of the Nissl substance during retrograde reaction is mediated through induced enzyme synthesis.

When the first injection of actinomycin is given 2 days after section of the nerve the neurons on the operated side show extreme chromatolysis 2 days later. This may indicate a more rapid turnover rate of the RNA of the finely dispersed cytoplasmic basophilic particles than of the large Nissl granules of normal neurons.

Keywords

Facial Nerve Actinomycin Intracerebral Injection Facial Nucleus Normal Neuron 
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.

Zusammenfassung

Die retrograden Zellveränderungen im Facialiskern der Maus wurden nach intracerebraler Injektion von Actinomycin D untersucht. Normalerweise zeigen diese Neurone erhöhte Basophilie des Cytoplasmas und abnehmende Größe der Nissl-Schollen während der ersten Tage nach Durchtrennung des Nerven. Der Nervenzelldurchmesser nimmt während des 2.–4. Tages nach der Nervendurchtrennung zu.

Nach intracerebraler Injektion von Actinomycin D kommt es zur raschen Desintegration der Nucleoli sämtlicher Neurone, während das Cytoplasma nur geringe Veränderungen aufweist. Die Nissl-Substanz der normalen Neurone erscheint 2 Tage nach der Behandlung gut erhalten.

Wird Actinomycin zum Zeitpunkt der Durchtrennung des N. facialis verabreicht, so sind alle Veränderungen der retrograden Zellveränderung während der folgenden 48 Std blockiert. Diese Befunde weisen darauf hin, daß die Auflösung der Nissl-Substanz im Rahmen der retrograden Zellreaktion durch eine induzierte Enzymsynthese vermittelt wird.

Wird die erste Actinomycin-Injektion 2 Tage nach der Nervendurchtrennung verabreicht, so zeigen die Neurone der durchtrennten Seite nach 2 Tagen extreme Chromatolyse. Das könnte auf eine raschere Übertragungsrate von RNS auf die fein verteilten basophilen Partikeln des Cytoplasmas als auf die großen Nissl-Granula der normalen Neurone hinweisen.

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References

  1. Amano, M.: Improved technique, for the enzymatic extraction of nucleic acids from tissue sections. J. Histochem. Cytochem.10, 204–212 (1962).Google Scholar
  2. Andres, K. H.: Untersuchungen über morphologische Veränderungen in Spinalganglien während der retrograden Degeneration. Z. Zellforsch.55, 49–79 (1961).Google Scholar
  3. Barondes, S. H., andM. E. Jarvik: The influence of actinomycin-D on brain RNA synthesis and on memory. J. Neurochem.11, 187–195 (1964).Google Scholar
  4. Bondy, S. C.: The ribonucleic acid, metabolism of the brain. J. Neurochem.13, 955–959 (1966).Google Scholar
  5. Brattgård, S. O., J. E. Edström, andH. Hydén: The chemical changes in regenerating neurons. J. Neurochem.1, 316–325 (1956/1957).Google Scholar
  6. Brockman, R. W., andE. P. Anderson: Biochemistry of cancer (metabolic aspects). Ann. Rev. Biochem.32, 463–512 (1963).Google Scholar
  7. Cammermeyer, J.: The importance of avoiding “dark” neurons in experimental neuropathology. Acta neuropath. (Berl.)1, 245–270 (1961).Google Scholar
  8. —: Peripheral chromatolysis after transection of mouse facial nerve. Acta neuropath. (Berl.)2, 213–230 (1963).Google Scholar
  9. Casperson, T. S., S. Farber, G. E. Foley, andD. Killander: Cytochemical observations on the nucleolus-ribosome system. Exp. Cell Res.32, 529–552, (1963).Google Scholar
  10. Chantrenne, H.: On the use of actinomycin for observing the turnover of ribonucleic acid. Biochim. biophys. Acta (Amst.)95, 351–353 (1965).Google Scholar
  11. Datta, R. K.: Brain ribosomes. Brain Res.2, 301–322 (1966).Google Scholar
  12. Evans, D. H. L., andE. G. Gray: Changes in the fine structure of ganglion cells during chromatolysis. In: Cytology of nervous tissue, pp. 71–74. Proc. Anat. Soc. Gr. Brit. and Irel. Taylor and Francis Ltd., London 1961.Google Scholar
  13. Geuskens, M.: Etude autoradiographique et ultrastructurale de l'action de l'actinomycine D sur les oocytes d'astérie. Exp. Cell Res.39, 400–412 (1965).Google Scholar
  14. Goldberg, I. H., andE. Reich: Actinomycin inhibtion of RNA synthesis directed by DNA. Fed. Proc.23, 958–964 (1964).Google Scholar
  15. Goldstein, M. N., I. J. Slotnick, andL. J. Journey:In vitro studies with HeLa cell lines sensitive and resistent to actinomycin D. Ann. N. Y. Acad. Sci.89, 474–483 (1960).Google Scholar
  16. Griffin, M. J., andR. P. Cox: Studies on the mechanism of hormonal induction of alkaline phosphatase in human cell cultures. 1. Effects of puromycin and actinomycin D. J. Cell Biol.29, 1–9 (1966).Google Scholar
  17. Hechter, O., andI. D. K. Halkerston: Effects of steroid hormones on gene regulation and cell metabolism. Ann. Rev. Physiol.27, 133–162 (1965).Google Scholar
  18. Honig, G. R., andM. Rabinovitz: Inhibition by actinomycin D of oxidation-dependent biosynthesis in Sarcoma 37 ascites cells. J. biol. Chem.241, 1681–1687 (1966).Google Scholar
  19. Karnofsky, D. A., andB. D. Clarkson: Cellular effects of anticancer drugs. Ann. Rev. Pharmacol.3, 357–428 (1963).Google Scholar
  20. Laszlo, J., D. S. Miller, K. S. McCarty, andP. Hochstein: Actinomycin D: Inhibition of respiration and glycolysis. Science151, 1007–1009 (1966).Google Scholar
  21. Loeb, J. N., R. R. Howell, andG. M. Tomkins: Turnover of ribosomal RNA in rat liver. Science149, 1093–1095 (1965).Google Scholar
  22. Mackey, E. A., D. Spiro, andJ. Wiener: A study of chromatolysis in dorsal root ganglia at the cellular level. J. Neuropath. exp. Neurol.23, 508–526 (1964).Google Scholar
  23. Pannese, E.: Investigations on the ultrastructural changes of spinal ganglion neurons in the course of axon regeneration and cell hypertrophy. I. Changes during axon regeneration. Z. Zellforsch.60, 711–740 (1963).Google Scholar
  24. Philips, F. S., H. S. Schwartz, S. S. Sternberg, andU. T. C. Tan: The toxicity of actinomycin D. Ann. N. Y. Acad. Sci.89, 348–360 (1960).Google Scholar
  25. Reicht, E.: Biochemistry of actinomycins. Cancer Res.23, 1428–1441 (1963).Google Scholar
  26. Revel, M., andH. H. Hiatt: The stability of liver messenger RNA. Proc. nat. Acad. Sci. (Wash.)51, 810–817 (1964a).Google Scholar
  27. ——: Actinomycin D: An effect on rat liver homogenates unrelated to its action on RNA synthesis. Science146, 1311–1313 (1964b).Google Scholar
  28. Reynolds, R. C., P. O'B. Montgomery, andB. Hughes: Nucleolar “caps” produced by actinomycin D. Cancer Res.24, 1269–1277 (1964).Google Scholar
  29. Samuels, L. D.: Actinomycin and its effects. Influence on an effector pathway for hormonal control. New Engl. J. Med.271, 1252–1258 (1964).Google Scholar
  30. Schoefl, G. I.: The effect of actinomycin D on the fine structure of the nucleolus. J. Ultrastruct. Res.10, 224–243 (1964).Google Scholar
  31. Schwartz, H., J. E. Södergren, M. Garafalo, andS. S. Sternberg: Actinomycin D. Effects on nucleic acid and protein metabolism in intact and regenerating liver of rats. Cancer Res.25, 307–317 (1965).Google Scholar
  32. Shatkin, A. J., E. Reich, R. M. Franklin, andE. L. Tatum: Effect of mitomycin C on mammalian cells in culture. Biochim. biophys. Acta (Amst.)55, 277–289 (1962).Google Scholar
  33. Stenram, U.: Radioautographic RNA and protein, labeling and the nucleolar volume in rats following administr. of moderate doses of actinomycin D. Exp. Cell Res.36, 242–255 (1964).Google Scholar
  34. Torvik, A., andA. Heding: Further observations on the effect of actinomycin D on retrograde nerve cell reaction. (In preparation.)Google Scholar
  35. Watson, W. E.: An autoradiographic study of the incorporation of nucleic acid precursors by neurons and glia during nerve regeneration. J. Physiol. (Lond.)180, 741–753 (1965).Google Scholar
  36. Weber, G., R. L. Singhal, N. B. Stamm, andS. K. Srivastava: Hormonal induction and suppression of liver enzyme biosynthesis. Fed. Proc.24, 745–754 (1965).Google Scholar
  37. Wiesner, R., G. Acs, E. Reich, andA. Shafiq: Degradation of ribonucleic acid in mouse fibroblasts treated with actinomycin. J. Cell Biol.27, 47–52 (1965).Google Scholar

Copyright information

© Springer-Verlag 1967

Authors and Affiliations

  • Ansgar Torvik
    • 1
  • Anna Heding
    • 1
  1. 1.Department of PathologyUllevål HospitalOslo

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