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Acta Neuropathologica

, Volume 26, Issue 3, pp 259–264 | Cite as

Neurotoxic effects of 6-aminonicotinamide on cultures of central nervous tissue

  • Seung U. Kim
  • Byron S. Wenger
Short Original Communications

Summary

Well myelinated cultures of chick embryo spinal cord were exposed to medium containing 6-aminonicotinamide in a concentration of 0.5 mmol for up to 48 h. By 24–48 h of exposure to the antivitamin, neurons showed a granulovacuolar degeneration which later led to the formation of large vacuoles in the neuronal perikarya. Myelin degeneration was also observed in this period in the form of swelling, beading and ballooning. Electron microscopy revealed moderately swollen mitochondria and dilated endoplasmic reticulum as the earliest neuronal change. Later, neurons became pyknotic and the cytoplasmic organelles disintegrated. Presynaptic endings and glial cells, however, was spared any degenerative change. Intermittent and irregular splitting of myelin lamellae were also observed along the intraperiod lines. Biochemical assay of the glucose-6-phosphate dehydrogenase activity in the experimental cultures showed that 45% of the enzyme activity was lost during the 30-h period. It is concluded that the formation of 6-aminonicotinamide analogues of NAD and NADP coenzymes leads to the impairment of the pentose phosphate pathway and the glucose turnover, and thus produces neurotoxic effects in the central nervous system.

Key words

6-Aminonicotinamide Tissue Culture of Chick Spinal Cord Electron Microscopy Neurotoxic Effects Glucose-6-Phosphate Dehydrogenase 

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References

  1. Bornstein, M. B. Murray, M. R.: Serial observations on patterns of growth, myelin formation, maintenance and degeneration in cultures of newborn rat and kitten cerebellum. J. biophys. biochem. Cytol.4, 499–504 (1958)Google Scholar
  2. Buell, M. V., Lowry, O. H., Roberts, N. R., Chang, M. W., Kapphahn, J. I.: The quantitative histochemistry of the brain. V. Enzymes of the glucose metabolism. J. biol. Chem.232, 979–993 (1957)Google Scholar
  3. Coper, H.: Disturbances in pyridine nucleotide metabolism of the central nervous system caused by nicotinamide antimetabolites. Biochem. J.106, 7–8p (1968)Google Scholar
  4. Coper, H., Herken, H.: Schädigung des Zentralnervensystems durch Antimetaboliten des Nikotinsäureamids. Dtsch. med. Wschr. 88, 2025–2036 (1963)Google Scholar
  5. Dietrich, L. S., Friedland, I. M., Kaplan, L. A.: Pyridine nucleotide metabolism: Mechanism of action of the niacin antagonist 6-aminonicotinamide. J. biol. Chem.233, 964–968 (1958)Google Scholar
  6. Herken, H., Lange, K.: Bloeking of pentose phosphate pathway in the brain of rats by 6-aminonicotinamide. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.263, 496–499 (1969).Google Scholar
  7. Johnson, W. J., McColl, J. D.: Antimetabolic activity of 6-aminonicotinamide. Fed. Proc.15, 284 (1965)Google Scholar
  8. Kim, S. U., Oh, T. H., Johnson, D. D.: Developmental changes of acetylcholinesterase and pseudocholinesterase in organotypic cultures of spinal cord. Exp. Neurol.35, 274–281 (1972)Google Scholar
  9. Schneider, H.: Schädigung der Formatio reticularis durch den Antimetaboliten 6-Aminonikotinsäureamid. In Proc. 6th Internat. Congr. Neuropath., pp. 135–136. Paris: Masson et Cie (1970)Google Scholar
  10. Schochet, S. S.: Pathogenesis of 6-aminonicotinamide neurotoxicity. Proc. 6 th Internat. Congr. Neuropath., pp. 89–90. Paris: Masson et Cie 1970Google Scholar
  11. Sternberg, S. S., Philips, F. S.: 6-aminonicotinamide and acute degenerative changes in the central nervous system. Science127, 644–646 (1958).Google Scholar
  12. Wolf, A, Cowen, D., Geller, L. M.: The effects of an antimetabolite, 6-aminonicotinamide. on the central nervous system. Trans. Amer. neurol. Assn.1659, 140–145Google Scholar
  13. Wolf, A., Cowen, D., Geller, L. M.: Structural and functional effects of 6-aminonicotinamide and other antimetabolites on the central nervous system. In: Proc. 4th Internat. Congr. Neuropath., pp. 447–453. F. Lüthy and A. Bischoff (Eds.). Zürich: Excerpta Medica Foundation 1966Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • Seung U. Kim
    • 1
    • 2
  • Byron S. Wenger
    • 1
  1. 1.Department of AnatomyUniversity of SaskatchewanCanada
  2. 2.Division of NeuropathologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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