Summary
Lesions in the CNS induced by 6-aminonicotinamide (6-AN) presented a spongy state of the gray matter and neuronal chromatolysis. With aging of the experimental animals the lesions extended from the phylogenetically early developed structures to those developed later, i.e., from spinal gray matter, dentate nuclei, and brain stem nuclei through limbic structures and striatum to the cerebral cortex. Changes of the neurons were more prominent with aging.
Lesions in the CNS of rats at the age, corresponding to the involutional period in the human, were similar to those of Creutzfeldt-Jakob disease (C-J disease) in the presenile age. In recent years, the resemblance between C-J disease and pellagra encephalopathy had been noted by several authors, and they resemble the lesions caused by 6-AN, an antimetabolite of nicotinamide used in our experiment. This evidence, therefore, has led to the hypothesis that dysfunction of NAD(H)- or NADP(H)-dependent enzymes in the CNS of the aged, even if not the primary cause, may be one possible pathogenetic factor of C-J disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Berl, S., Clarke, D. D.: Compartmentation of amino acid metabolism. In: Handbook of neurochemistry, Lajtha, A. (ed.), Vol. 2, pp. 447–472. New York: Plenum Press 1969
Bielicki, L., Krieglstein, J.: Decreased GABA and glutamate concentration in rat brain after treatment with6-aminonicotinamide. Naunyn-Schmiedebergs Arch. Pharmacol.294, 157–160 (1976)
Bignami, A., Forno, L. S.: Status spongiosus in Jakob-Creutzfeldt disease: Electron microscopic study of a cortical biopsy. Brain93, 89–94 (1970)
Coper, H., Herken, H.: Schädigung des Zentralnervensystems durch Antimetaboliten des Nikotinsäureamids. Ein Beitrag zur Molekularpathologie der Pyridinnukleotide. Dtsch. Med. Wochenschr.88, 2025–2036 (1963)
Denton, J.: A study of tissue changes in experimental black tongue in dogs compared with similar changes in pellagra. Am. J. Path.4 341–352 (1928)
Farris, E. J.: The rats as an experimental animal. In: The care and breeding of laboratory animals, Farris, E. J., et al. (eds.), pp. 43–78. New York, London, Sydney: Wiley 1950
Fisher, H. F.: Glutamate dehydrogenase — Ligand complexes and their relationship to the mechanism of the reaction. In: Advances in enzymology, Meister, A. (ed.), Vol. 39, pp. 369–417. New York, London, Sydney, Toronto: Wiley 1973
Gibbs, C. J., Gajdusek, D. C., Asher, D. M., Alpers, M. P., Beck, E., Daniel, P. M., Matthews, W. B.: Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science161, 388–389 (1968)
Gonatas, N. K., Terry, R. D., Weiss, M.: Electron microscopic study in two cases of Jakob-Creutzfeldt disease. J. Neuropathol. Exp. Neurol.24, 575–598 (1965)
Harris, B.: Cortical alterations due to methionine sulfoximine. Ultrastructure during seizure activity. Arch. Neurol.11, 388–407 (1964)
Horita, N., Oyanagi, S., Ishii, T., Izumiyama, Y.: Ultrastrucure of 6-aminonicatinamide (6-AN)-induced lesions in the central nervous system of rats. 1. Chromatolysis and other lesions in the cervical cord. Acta Neuropathol. (Berl.)44, 111–119 (1978)
Horita, N., Ishii, T., Izumiyama, Y.: Ultrastrucure of 6-aminonicotinamide (6-AN)-induced lesions in the central nervous system of rats. III. Alterations of the lumbal cord lesions with aging 17th Congress of Jap. Neuropath. Soc., Maebashi 1979
Jacob, H.: Differentialdiagnose perniciöser Involutionspsychosen, präseniler Psychosen bei Involutionspellagra. Zur Frage endogen-exogener Mischbilder (Intermediärsyndrome) im höheren Lebensalter. Arch. Psychiatr. Nervenkr.201, 17–52 (1960)
Jervis, G. A., Hurdum, H. M., O'Neill, F. J.: Presenile psychosis of the Jakob type. Clinico-pathologic study of one case with a review of the literature. Am. J. Psychiatry99, 101–109 (1942)
Johnson, M. K., Barnes, J. M.: Age and the sensitivity of chicks to the delayed neurotoxic effects of some organophosphorous compounds. Biochem. Pharmacol.19, 3045–3047 (1970)
Kidd, M.: Some electron microscopical observation on status spongiosus. Acta Neuropathol. (Berl.) [Suppl. 3] 137–144 (1967)
Lange, K., Kolbe, H., Keller, K., Herken, H.: Der Kohlenhydrat-stoffwechsel des Gehirns nach Blockade des Pentose-Phosphat-Weges durch 6-Aminonicotinsäureamid. Hoppe Seylers Z. Physiol. Chem.351, 1241–1252 (1970)
Lemkey-Johnston, N., Reynolds, W. A.: Nature and extent of brain lesions in mice related to ingestion of monosodium glutamate. A light and electron microscope study. J. Neuropathol. Exp. Neurol.33, 74–97 (1974)
Lierse, W.: Ultrastrukturelle Hirnveränderungen der Ratte nach Gaben von 3-Acetylpyridin. Z. Zellforsch.67, 86–95 (1965)
McGeer, E., McGeer, P. L.: Neurotransmitter metabolism in the aging brain. In: Aging, Vol. 3, Neurobiology of aging, Terry, R. D., Gershon, S. (eds.), pp. 389–403. New York: Raven Press 1976
McIlwain, H., Bachelard, H. S.: Biochemistry and the central nervous system. 4th ed. Edinburgh, London: Churchill Livingstone 1971
Meier-Ruge, W., Reichlmeier, K., Iwangoff, P.: Enzymatic and enzyme histochemical changes of the aging animal brain and consequences for experimental pharmacology on aging. In: Aging. Vol. 3, Neurobiology of the aging, Terry, R. D., Gershon, S. (eds.), pp. 379–387. New York: Raven Press 1976
Norenberg, M. D.: Histochemical studies in experimental portalsystemic encephalopathy. 1. Glutamic dehydrogenase. Arch. Neurol.33, 265–269 (1976)
Norenberg, M. D., Lapham, L. W.: The astrocyte response in experimental portal-systemic encephalopathy: An electron microscopic study. J. Neuropathol. Exp. Neurol.33, 422–435 (1974)
Olney, J. W.: Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J. Neuropathol. Exp. Neurol.30, 75–90 (1971)
Persson, L., Wingren, U., Kristensson, K.: Hexachlorophene-induced lesions in the developing peripheral nervous system of mice. Neuropathol. Appl. Neurobiol.2, 167–174 (1976)
Rasul, A. R., Howell, J. McC.: A comparison of the effect of sodium diethyldithiocarbamate on the central nervous system of young and adult domestic fowl. Acta Neuropathol. (Berl.)24, 68–75 (1973)
Rizzuto, N., Gonatas, N. K.: Ultrastructural study of effect of methionine sulfoximine on developing and adult rat cerebral cortex. J. Neuropathol. Exp. Neurol.33, 237–250 (1974)
Smith, W. T.: Nutritional deficiencies and disorders. In: Greenfield's neuropathology, 3rd ed., Blackwood, W., Corsellis, J. A. N., McMenemey, W. H. (eds.), pp. 194–237. Edinburgh: Arnold 1976
Stadler, H.: Über Beziehungen zwischen Creutzfeldt-Jakobscher Krankheit (spastische Pseudosklerose) und Pellagra. Z. Gesamte Neurol. Psychiatr.165, 326–332 (1939)
Towfighi, J., Gonatas, N. K.: Effect of intracerebral injection of ouabain in adult and developing rats. Lab. Invest.28, 170–180 (1973)
Zamora, A. J., Cavanagh, J. B., Kyu, M. H.: Ultrastructural responses of the astrocytes to portocaval anastomosis in the rat. J. Neurol. Sci.18, 25–45 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Horita, N., Ishii, T. & Izumiyama, Y. Ultrastructure of 6-aminonicotinamide (6-AN)-induced lesions in the central nervous system of rats. Acta Neuropathol 49, 19–27 (1980). https://doi.org/10.1007/BF00692215
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00692215