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.
References
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)
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)
Coper, H.: Disturbances in pyridine nucleotide metabolism of the central nervous system caused by nicotinamide antimetabolites. Biochem. J.106, 7–8p (1968)
Coper, H., Herken, H.: Schädigung des Zentralnervensystems durch Antimetaboliten des Nikotinsäureamids. Dtsch. med. Wschr. 88, 2025–2036 (1963)
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)
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).
Johnson, W. J., McColl, J. D.: Antimetabolic activity of 6-aminonicotinamide. Fed. Proc.15, 284 (1965)
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)
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)
Schochet, S. S.: Pathogenesis of 6-aminonicotinamide neurotoxicity. Proc. 6 th Internat. Congr. Neuropath., pp. 89–90. Paris: Masson et Cie 1970
Sternberg, S. S., Philips, F. S.: 6-aminonicotinamide and acute degenerative changes in the central nervous system. Science127, 644–646 (1958).
Wolf, A, Cowen, D., Geller, L. M.: The effects of an antimetabolite, 6-aminonicotinamide. on the central nervous system. Trans. Amer. neurol. Assn.1659, 140–145
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 1966
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kim, S.U., Wenger, B.S. Neurotoxic effects of 6-aminonicotinamide on cultures of central nervous tissue. Acta Neuropathol 26, 259–264 (1973). https://doi.org/10.1007/BF00684436
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00684436