Animal Models of Niacin-Nicotinamide Deficiency

  • Frederick C. Kauffman
Part of the Neuromethods book series (NM, volume 22)


The human disease caused by niacin (vitamin B3) deficiency is pellagra, a disease that at one time filled insane asylums all over the world before the function of niacin was discovered. The recognition of pellagra as an endemic disease in the US dates from Searcy’s report in 1907 (Strandell et al., 1989) describing 88 cases of dementia in the Mount Vernon, Alabama Insane Asylum. Extensive knowledge about the course of pellagra has since been obtained and this disease has been eradicated as a public health problem; however, exact relationships between niacin deficiency and specific lesions in the central nervous system (CNS) remain poorly defined. Other nutritional deficiencies, common among patients in mental hospitals and in those with senility (Gregory, 1955; Hersov, 1955; McIlwain, 1966), undoubtedly contribute to neuronal dysfunction and exacerbate neurological problems associated with niacin deficiency. Mental symptoms associated with niacin deficiency often precede the dermatitis and other effects of this nutritional deficiency, suggesting a special sensitivity of the nervous system. If initial mental disturbances are not remedied by administration of nicotinic acid or tryptophan, from which nicotinic acid is synthesized in vivo, permanent structural changes occur in cerebral tissue.


Pentose Phosphate Pathway Quinolinic Acid Nicotinamide Adenine Dinucleotide Cerebral Tissue Pyridine Nucleotide 
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.


  1. Adams D. A., Smith S. J., and Thompson S. H. (1980) Ionic currents in molluscan soma. Ann. Rev. Neurosci. 3,141–167.PubMedGoogle Scholar
  2. Axelrod A. E., Spies T. D, and Elvehjam C. A. (1941) The effect of a nicotinic acid deficiency upon the coenzy me I content of the human. J. Biol. Chem. 138,667–676.Google Scholar
  3. Badawy A. A.-B,, Morgan C. J., Lane J., Dhaliwal K., and Bradley D. M. (1989) Liver tryptophan pyrrolase. A major determinant of the lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL mice. Biochem. J. 264, 597–599.PubMedGoogle Scholar
  4. Bain J. A. and Pollock G. H. (1949) Normal and seizure levels of lactate, pyruvate and acid soluble phosphates in the cerebellum and cerebrum. Proc. Soc. Exp. Biol. Med. NY 71, 495–497.Google Scholar
  5. Balazs R., Machiyama Y., Hammond B. J., Julian T., and Richter D. (1970) The operation of the gamma-aminobutyrate bypath of the tricarboxy-lic acid cycle in brain tissue in vitro. Biochem. J. 116, 445–467.PubMedGoogle Scholar
  6. Bender D. A., Smith W. R. D., and Humm R. P. (1977) Effects of benserazide on tryptophan metabolism in the mouse. Biochem Pharmcol. 26, 1619–1623.Google Scholar
  7. Bielicki L. and Krieglstein J. (1976) Inhibition of glucose phosphorylation in rat brain by thiopental. Naunyn-Schmied. Arch. Pharmacol. 293, 25–29.Google Scholar
  8. Blackwood W., McMenemey W. H., Meyer A., Norman R. M., and Russell D. S. (1963) Greenfield’s Neuropathology. Arnold, London.Google Scholar
  9. Boegman R. J. and Albuquerque E. X. (1980) Axonal transport in rats ren dered paraplegic following a single subarachnoid injection of either batrachotoxin or 6-amino-nicotinamide into the spinal cord. J. Neurobiol. 11, 283–290.PubMedGoogle Scholar
  10. Booth R. F. G. and Clarke J. B. (1978) The control of pyruvate dehydrogenase in isolated brain mitochondria. J. Neurochem. 30, 1003–1008.PubMedGoogle Scholar
  11. Brown O. R. and Seither R. L. (1989) Paraquat inhibits NAD biosynthesis at the quinolinic acid synthetase site. Med. Sci. Res. 17, 819–820.Google Scholar
  12. Brunink H. and Wessels E. J. (1972) The determination of nicotinic acid by fluorometric densitometry. Analyst 97, 258,259.Google Scholar
  13. Bruyn R. P. M. and Stoof J. C. (1990) The quinolinic acid hypothesis in Huntington’s chorea. J. Neurol. Sci. 95,29–38.PubMedGoogle Scholar
  14. Brzoska H.-R. and Adhami H. (1975) Electron microscopic study of the effect of 6-AN on the sciatic nerve in newborn rats. Acta Neuropathol. 33 59–6PubMedGoogle Scholar
  15. Buell M. V., Lowry O. R, Roberts N. R., Chang M-L. W., and Kapphahn J. I. (1958) The quantitative histochemistry of the brain. V. Enzymes of glucose metabolism. J. Biol. Chem. 232, 979–993.PubMedGoogle Scholar
  16. Burch H. B., Lowry O. H., Padilla A. M., and Combs A. M. (1956) Effects of riboflavin deficiency and realimentation on flavin enzymes of tissues. J. Biol. Chem. 233, 29–45.Google Scholar
  17. Carpenter K. I. (1981) Effects of different methods of processing maize on its pellagragenic activity. Fed. Proc. 40, 1531–1535.PubMedGoogle Scholar
  18. Chamberlain J. G. and Nelson M. M. (1963) Multiple congenital abnormalities in the rat resulting from acute maternal niacin deficiency during pregnancy. Proc Soc. Exp Biol. Med 112, 836–840.PubMedGoogle Scholar
  19. Chamberlain J. G. (1972) 6-Aminonicotinamide (6AN)-induced abnormali-ties of the developing ependyma and choroid plexus as seen with the scanning electron microscope. Teratology 6, 281–286.PubMedGoogle Scholar
  20. Chui E. and Garcia H. J. (1979) Pathogenesis of 6aminonicotinamide neurotoxicity: New structural analysis, in Progress in Neuropathology, vol.4 (ZimmermanH. M., ed.), Raven Press,New York, pp. 341–359Google Scholar
  21. Churchill L., Dilts R. P., and Kalivas P. W. (1990) Changes in garnmaaminobutyric acid, μ-opioid and neurotensin receptors in the accumbens-pallidal projection after discrete quinolinic acid lesions in the nucleus accumbens. Brain Res. 511, 41–54.PubMedGoogle Scholar
  22. Clark B. R., Halpern R. M., and Smith R. A. (1975) A fluorimetric method for quantitation in the picomole range of N1-methylnicotinamide and nicotinamide in serum. Anal. Biochem. 68, 54–61PubMedGoogle Scholar
  23. Coggeshall R. E. and MacLean P. D. (1958) Hippocampal lesions following administration of 3-acetylpyridine. Proc. Soc. Exp. Biol. Med. 98, 687–689.PubMedGoogle Scholar
  24. Coper H., Hadass H., and Lison H. (1966) Untersuchungen zum mechanismus zentralnervoser funktionsstorungen durch 6-aminonicotinamid. Naunyn-Schmied. Arch. Pharmakol. Exp. Pathol. 255, 96–106.Google Scholar
  25. D’Adamo A. F., Jr. and Haft D. E. (1965) An alternate pathway of alphaketoglutarate catabolism in the isolated, perfused rat liver. I. Studies with DL-glutamate-2-and-5-14C. J Biol. Chem 240, 613–617.Google Scholar
  26. Deguchi T., Ichiyama A., Nishizuka Y., and Hayaishi O. (1968) Studies on the biosynthesis of nicotinamide adenine dinucleotide in the brain. Biochim. Biophys Acta 158, 382–393.PubMedGoogle Scholar
  27. Denson R. (1962) Nicotinamide in the treatment of schizophrenia. Dis Nerv. Syst. 23, 162–172.Google Scholar
  28. Desclin J. C. and Escubi J. (1974) Effects of 3-acetylpyrine on the CNS of the rat, as demonstrated by silver methods. Brain Res. 77,349–364.PubMedGoogle Scholar
  29. Deshpande S. S., Albuquerque E. X., Kauffman F. C., and Guth L. (1978) Physiological, biochemical and histological changes in skeletal muscle, neuromuscular junction and spinal cord of rats rendered paraplegic by subarachnoidal administration of 6-aminonicotinamide. Brain Res. 140, 89–109.PubMedGoogle Scholar
  30. Deutch A. Y., Rosin D. L., Goldstein M., and Roth R. H. (1989) 3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system: An animal model of olivopontocerebellar atrophy-associated Parkinsonism. Exp. Neural. 105, 1–9.Google Scholar
  31. Dorris R. L. (1989) Interactions of nicotinamide with dopamine receptors in vivo. Pharmacol. Biochem. Behav. 33,915–917.PubMedGoogle Scholar
  32. Dickens F. and Glock G. E. (1951) Direct oxidation of glucose-6-phosphate, 6-phosphogluconate and pentosed-phosphates by enzymes of animal origin. Biochem. J. 50,81–95.PubMedGoogle Scholar
  33. Edstrom J.-E. and Grampp W. (1965) Nervous activity and metabolism of ribonucleic acids in the crustacean stretch receptor neuron. J. Neurochem. 12,735–741.PubMedGoogle Scholar
  34. Fenerty C. A. and Lindup W. E. (1989) Brain uptake of L-tryptophan and diazepam: The role of plasma protein binding. J Neurochem. 53, 416–422.PubMedGoogle Scholar
  35. Frieda R. L. and Bischhausen R. (1978) How do axons control myelin formation? The model of 6-aminonicotinamide neuropathy. J. Neural. Sci. 35, 341–353.Google Scholar
  36. Gal E. M. (1974) Cerebral tryptophan-2,3-dioxygenase (pyrrolase) and its induction in rat brain, J. Neurochem. 22, 861–863.PubMedGoogle Scholar
  37. Gallent M., Bishop M., and Steele G. (1966) DPN (NAD oxidized form): A preliminary evaluation in chronic schizophrenic patients. Ann. Ther. Res. 8, 542.Google Scholar
  38. Garcia-Bunuel L., McDougal D. B., Jr., Burch H. B., Jones E. M., and Touhill E. (1962) Oxidized and reduced pyridine nucleotide levels and enzyme activities in brain and liver of niacin deficient rats. J. Neurochem. 9, 589–594.PubMedGoogle Scholar
  39. Genazzani E. and Di Carlo R. (1974) Inference of neurologically active drugs with metabolism of RNA in brain, in Central Nervous System. Studies on Metabolic Regulation and Function (Genazzani E. and Herken H., eds.), Springer-Verlag, Berlin pp.217–222.Google Scholar
  40. Gerber G. B. and Demo J. (1970) Metabolism of labelled nicotinamide coenzyme in different organs of mice and rats. Proc. Soc. Exp. Biol. Med. 134,689–693.PubMedGoogle Scholar
  41. Gibson G. E., Glantz S., Duffy T. E., and Blass J. P. (1983) Regional brain glucose utilization and behavior during niacin deficiency. Trans. Am. Soc. Neurochem. 14, 121.Google Scholar
  42. Clock G. E., and McLean P. (1954) Levels of enzymes of the direct oxidative pathway of carbohydrate metabolism in mammalian tissues and tumours. Biochem J. 56, 171–175.Google Scholar
  43. Goldsmith G. A. (1958) Niacin-tryptophan relationships in man and niacin requirement. Am. J. Clin. Nutr. 6, 479–486.PubMedGoogle Scholar
  44. Grant W. M. (1980) The peripheral visual system as a target, in Experimental and Clinical Neurotoxicology (Spencer P. S. and Schaumburg H. H., eds.), Williams and Wilkins, Baltimore, pp.77–91.Google Scholar
  45. Gregory I. (1955) The role of nicotinic acid (niacin) in mental health and disease. J. Merit. Sci. 101,85–109.Google Scholar
  46. Griffiths I. R., Kelly P. A. T., and Grome J. J. (1981) Glucose utilization in the CNS in the acute gliopathy due to 6-aminomcotinamide. Lab. Invest. 44, 547–552.PubMedGoogle Scholar
  47. Harkonen M. A. and Kauffman F. C. (1974) Metabolic alterations in the axotomized superior cervical ganglion of the rat. II. The pentose phosphate pathway. Brain Res. 65, 141–157.PubMedGoogle Scholar
  48. Hayes W. J., Jr. (1982) Pesticides Studied in Man. Williams and Wilkins, BaltimoreGoogle Scholar
  49. Heald P. J. (1956) Effects of electrical pulses on the distribution of radioactive phosphate in cerebral tissue. Biochem. J. 63,242–249.PubMedGoogle Scholar
  50. Herken H., Lange K., and Kolbe H. (1969) Brain disorders induced by pharmacological blockade of the pentose phosphate pathway. Biochem. Biophys. Res. Commun. 36, 93–100.PubMedGoogle Scholar
  51. Herken H. (1970) Antimetabolic action of 6aminonicotinamide on the pentose phosphate pathway in the brain, in A Symposium on Mechanisms of Toxicity (Aldridge W. N., ed.), MacMillan, London, pp. 189–203.Google Scholar
  52. Herken H., Lange K., Kolbe H., and Keller K. (1974) Antimetabolic action of the pentose phosphate pathway in the entral nervous sytem induced by 6-aminonicotinamide, in Central Nervous System. Studies on Metabolic Regulation and Function (Genazzani E, and Herken H., eds.), Springer-Verlag, Berlin, pp. 41–54.Google Scholar
  53. Herken H., Meyer-Estorf G., Halbhubner K., and Loos D. (1976) Spastic paresis after 6-aminonicotinamide: Metabolic disorders in the spinal cord and electromyographically recorded changes in the hind limbs of rats. Naunyn-Schmied. Arch. Pharmacol. 293, 245–255.Google Scholar
  54. Hermann A. and Gorman A. L. F. (1981) Effects of 4-aminopyridine on potassium currents in a molluscan neuron. J. Gen. Physiol. 78, 63–86.PubMedGoogle Scholar
  55. Hersov L. A. (1955) A case of childhood pellagra with psychosis. J. Ment. Sci. 101, 878–883.PubMedGoogle Scholar
  56. Heyes M. P., Rubinow D., Lane G, and Markey S. P. (1989a) Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. Ann. Neural. 26, 275–277.Google Scholar
  57. Heyes M. P., Quearry B. J., and Markey S. P. (1989b) Systemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3 hydroxykynurenine and quinolinic acid content of mouse cerebral cortex. Brain Res. 49l, 173–179.Google Scholar
  58. Hicks S. P. (1955) Pathological effects of antimetabolites. I. Acute lesions in the hypothalamus, peripheral ganglia, and adrenal medulla caused by 3-acetylpyridine and prevented by nicotinamide. Am. J. Pathol. 31, 189–199.PubMedGoogle Scholar
  59. Himwich H. E. (1951) Brain Metabolism and Cerebral Disorders. Williams and Wilkins, Baltimore, MD.Google Scholar
  60. Hoffer A. (1962) Niacin Therapy in Psychiatry. Charles C. Thomas, Springfield, ILGoogle Scholar
  61. Hoffer A. (1966) The effect of nicotinic acid on the frequency and duration of rehospitalization of schizophrenic patients, a controlled comparison study. Int. J. Neuropsychtr. 2, 234–240.Google Scholar
  62. Horita N., Ishii T., and Izumiyama Y. (1981) Ultrastructure of 6-aminonicotinamide (6-AN)-induced lesions in the CNS of rats. III. Alterations of the spinal gray matter lesions with aging. Acta Neuropathol. 53, 227–235.PubMedGoogle Scholar
  63. Hothersall J. S., Baquer N. Z., Greenbaum A. L., and McLean P. (1979) Alternative pathways of glucose utilization in brain. Changes in the pattern of glucose utilization in brain during development and the effect of phenazine methosulfate on the integration of metabolic routes. Arch. Biochem. Biophys. 198, 478–492.PubMedGoogle Scholar
  64. Hothersall J. S., Zubairu S., McLean P., and Greenbaum A. L. (1981) Alternative pathways of glucose utilization in brain; Changes in the pattern of glucose utilization in brain resulting from treatment of rats with 6-aminonicotmamide. J. Neurochein. 37, 1484–1496.Google Scholar
  65. Hyden H. and Egyhazi E. (1968) The effect of tranylcypromine on synthesis of macromolecules and enzyme activities in neurons and glia. Natrology 18, 732–736.Google Scholar
  66. Ikeda M., Tsuji H., Nakamura S., Ichiyama A., Nishizuka Y., and Hayaishi O. (1965) Studies on the biosynthesis of nicotinamide adenine dinucle-otide. II. A role of picolinic carboxylase in the biosynthesis of nicoti-namide adenine dinucleotide from tryptophan in mammals. J. Biol. Chem. 240, 1395–1401.PubMedGoogle Scholar
  67. Jacobs J. M., Miller R. H., Whittle A., and Cavanagh J. B. (1979) Studies on the early changes in acute isoniazid neuropathy in the rat. Acta Neuropathol. 47, 85–92.PubMedGoogle Scholar
  68. Jepson J. B. (1972) Hartnup disease, in The Metabolic Basis of lnherited Disease (Stanbury J. B., Wyngaarden J. B., and Frederickson D. S., eds.), McGraw Hill, New York, pp. 1486–1503.Google Scholar
  69. Johnson W. J. and McCall J. D. (1955) 6-Aminonicotinamide, a potent nicotinamide antagonist. Science 122, 834.PubMedGoogle Scholar
  70. Kahana S. E., Lowry O. H., Schulz D. W., Passonneau J. V., and Crawford E. J. (1960) The kinetics of phosphoglucoisomerase. J. Biol. Chem. 235, 2178–2184.PubMedGoogle Scholar
  71. Kaplan N. O., Goldin A., Humphreys S. R., Ciotti M. M., and Stolzenbach F. E. (1956) Pyridine nucleotide synthesis in the mouse. J. Biol. Chem. 219, 287–298.PubMedGoogle Scholar
  72. Kaplan N. O. (1960) Neurochemistry of Nucleotides and Amino Acids (Brady R. O. and Tower D. B., eds.), Wiley, New York, pp. 41–54.Google Scholar
  73. Kauffman F. C. (1972) The quantitative histochemistry of enzymes of the pentose phosphate pathway in the CNS of the rat. J. Neurochem. 19, 1–9.PubMedGoogle Scholar
  74. Kauffman F. C. and Johnson E. C. (1974) Cerebral energy reserves and gly-colysis in neural tissue of 6-aminonicotinamide-treated mice. J. Neurobiol. 5, 379–392.PubMedGoogle Scholar
  75. Keller K., Kolbe H., Herken H., and Lange K. (1976) Glycolysis and glyco-gen metabolism after inhibition of hexose monophosphate pathway in C6-glial cells. Naunyn-Schmied. Arch. Pharmacol. 294, 213–215.Google Scholar
  76. Kline N. S., Barclay G. L., Cole J. O., Esser A. H., Lehmann H., and Wittenborn J. R. (1967) Diphosphopyridine nucleotide (DPN) in the treatment of schizophrenia. J. Am. Med. Assoc. 200, 881–882.Google Scholar
  77. Knoll-Kohler E., Wojnorowicz F., and Sarkander H.-J. (1980) Correlated changes in neuronal cerebral rat brain RNA synthesis and hypo-and hypermotoric disorders induced by 6-aminonicotinamide (6-AN). Exp. Brain Res. 38, 173–179.PubMedGoogle Scholar
  78. Kodicek E., Braude R., Kon S. K., and Mitchell K. G. (1959) The availability to pigs of nicotinic acid in tortilla baked from maize treated with lime-water. Br.J. Nutr. 13, 363–384.PubMedGoogle Scholar
  79. Kohler E., Barrach H-J., and Neubert D. (1970) Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analog of NADP. FEBS Lett. 6, 225–228.PubMedGoogle Scholar
  80. Krehl W. A., Teply L. J., and Elvehjem C. A. (1945) Corn as an etiological factor in the production of nicotinic acid deficiency in the rat. Science 101, 283.PubMedGoogle Scholar
  81. Krehl W. A. (1981) Discovery of the effect of tryptophan on niacin deficiency. Fed. Proc. 40, 1527–1530.PubMedGoogle Scholar
  82. Krieglstein J. and Stock R. (1975) Decreased glycolytic flux rate in the isolated perfused rat brain after pretreatment with 6-aminonicotinamide. Naunyn-Schinied. Arch. Pharmacol. 290, 323–327.Google Scholar
  83. Kuhlman R. E. and Lowry O. H. (1956) Quantitative histochemical changes during the development of the rat cerebral cortex. J. Neurochem. 1, 173–180.PubMedGoogle Scholar
  84. Laatsch R. H. (1962) Glycerol phosphate dehydrogenase activity of developing rat CNS. J. Neurochem. 9, 487–492.PubMedGoogle Scholar
  85. Laguna J. and Carpenter K. J. (1951) Raw versus processed corn in niacin-deficient diets. J. Nutr. 45, 21–28.PubMedGoogle Scholar
  86. Lajtha A. L., Maker H. S., and Clarke D. D. (1981) Metabolism and transport of carbohydrates and amino acids, in Basic Neurology (Siegel G. J., Albers R. W., Agranoff B. W., and Katzman R., eds.), Little, Brown, Boston, MA, pp.41–54.Google Scholar
  87. Lange K., Kolbe H., Keller K., and Herken H. (1970) Der kohlenhydratstof fwechsel des gehims nach blockade des pentose-phosphat-weges durch 6-aminonicotinsaureamid. Hoppe-Seyler’s Z. Physiol. Chein. 351, 1241–1252.Google Scholar
  88. Lapin I. P. (1978) Stimulant and convulsive effects of kynurenines injected into brain ventricules in mice. J. Neural Transm. 42, 37–43.PubMedGoogle Scholar
  89. Llinas R., Walton K., Hillman D. E., and Sotelo C. (1975) Inferior olive: Its role in motor learning. Science 190, 1230,1231.Google Scholar
  90. Llinas R., Walton K., and Bohr V. (1976) Synaptic transmission in squid giant synapse after potassium conductance blockage with external 3-and 4-aminopyridine. Biophys. J. 16, 83–86.PubMedGoogle Scholar
  91. Lowry O. H. and Passonneau J. V. (1964) The relationships between substrates and enzymes of glycolysis in brain. J. Biol. Chem. 239, 31–42.PubMedGoogle Scholar
  92. Luine V. N., and Kauffman F. C. (1971) Triphosphopyridine nucleotidede-pendent enzymes in the developing spinal cord of the rabbit. J. Neurochem. l8, 1113–1124.Google Scholar
  93. Madsen J., Abraham S., and Chaikoff I. L. (1964) The conversion of glutamate carbon to fatty acid carbon via citrate. I. The influence of glucose in lactating rat mammary gland slices. J. Biol. Chem. 239, 1305–1309.PubMedGoogle Scholar
  94. McCandless D. W. and Scott W. J. (1981) The effect of 6-aminonicotinamide on energy metabolism in rat embryo neural tube. Teratology 23, 391–395.PubMedGoogle Scholar
  95. McDougal D. B., Jr., Schultz D. W., Passonneau J. V., Clark J. R., Reynolds M. A., and Lowry O. H. (1961) Quantitative studies of white matter. I. Enzymes involved in glucose-6-phosphate metabolism. J. Gen. Physiol. 44, 487–498.PubMedGoogle Scholar
  96. McIlwain H. and Rodnight R. (1949) Breakdown of cozymase by a system from nervous tissue. Biochem. J. 44, 470–477.Google Scholar
  97. McIlwain H. (1966) Biochemistry and the CNS. J & A Churchill, London, pp. 102–126.Google Scholar
  98. Meyer-Estorf G., Schulze P. E., and Herken H. (1973) Distribution of 3H-labelled 6-aminonicotinamide and accumulation of 6-phosphoglu-conate in the spinal cord. Naunyn-Schmied. Arch. Phrmacol. 276, 235–241.Google Scholar
  99. Meyer-Konig E. (1973) Ultrastruktur der Glia-und Axonschadigung durch 6-Aminonicotinamid (6-AN) am Sehnerv der Ratte. Acta Neuropathol. 26, 115–126.PubMedGoogle Scholar
  100. Mosher L. R. (1970) Nicotinic acid side effects and toxicity: A review. Am. J. Psychiatr. 126, 1290–1296.PubMedGoogle Scholar
  101. Nakamura S., Ikeda M., Tsuji H., Nishizuka Y., and Hayaishi O. (1963) Quinolinate transphosphoribosylase: A mechanism of niacin ribonucle-otide formation from quinolinic acid. Biochem Biophys. Res. Commun. 13, 285–290.Google Scholar
  102. Nemeth A. M. and Dickerman H. (1960) Pyridine nucleotides and diphosphopyridine nucleotidase in developing mammalian tissues. J. Biol. Chem. 235, 1761–1764.PubMedGoogle Scholar
  103. Nisslbaum J. S., Packer D. E., and Bodansky O. (1964) Comparison of the actions of human brain, liver, and heart lactic dehydrogenase variants on nucleotide analogs and on substrate analogs in the absence and in the presence of oxalate and oxamate. J. Biol. Chem. 239, 2830–2834.Google Scholar
  104. Osmond H. and Hoffer A. (1962) Massive niacin treatment of schiiophrenia: Review of a nine year study. Lancet 1, 316–319.PubMedGoogle Scholar
  105. Perkins M. N. and Stone T. W. (1983) Quinolinic acid: Regional variations in neuronal sensitivity. Bruin Res. 259, 172–176.Google Scholar
  106. Pfeiffer C. C. (1981) Extranutrients and mental illness. Biol. Psychiatr. 16, 797–799.Google Scholar
  107. Plaitakis A., Nicklas W. J., and Desnick R. J. (1980) Glutamate dehydrogenase deficiency in three patients with spinocerebellar syndrome. Ann. Neural. 7, 297–303.Google Scholar
  108. Politis M. J. (1989) 6-Aminonicotinamide selectively causes necrosis in reactive astroglia cells in vivo. Preliminary morphological observations. J. Neural. Sci. 92, 71–79.Google Scholar
  109. Prakash M. R. and Baquer N. Z. (1981) Inhibition of gamma-aminobutyric acid transaminase with 6-aminonicotinamide in regions of the rat brain. Biochem. Pharmacol. 30, 663–664.PubMedGoogle Scholar
  110. Salter M., Knowles R. G., and Pogson C. I. (1989) How does displacement of albumin-bound tryptophan cause sustained increases in the free tryptophan concentration in plasma and 5-hydroxytryptamine synthesis in brain? Biochem.J. 262, 365–368.PubMedGoogle Scholar
  111. Samson F. E. Jr., and Dahl N. A. (1957) Cerebral energy requirement of neonatal rats. Am. J. Physiol. 188, 277–280.PubMedGoogle Scholar
  112. Sanberg P. R., Calderon S. F., Giordano M., Tew J. M., and Norman A. B. (1989) The quinolinic acid model of Huntington’s disease: Locomotor abnormalities. Exp. Neural. 105, 45–53.Google Scholar
  113. Sarkander H.-I., Knoll-Kohler E., and Cervos-Navarro J. (1978) Repression of glial RNA transcription during the development of 6-aminonicotinamide (6-AN)-induced acute gliopathy. J. Pharmacol. Exp. Ther. 205, 503–514.PubMedGoogle Scholar
  114. Schneider H. and Cervos-Navarro J. (1974) Acute gliopathy in spinal cord and brain stem induced by 6aminonicotinamide. Acta Neuropthal. 27,11–23.Google Scholar
  115. Schwartz R., Whetsell W. O., Jr., and Mangano R. M. (1983) Quinolinic acid: An endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219, 316–318.Google Scholar
  116. Singal S. A., Sydenstricker V. P., and Littlejohn J. M. (1948) The nicotinic acid content of tissues of rats on corn rations. J. Biol. Chem. 176, 1069–1073.PubMedGoogle Scholar
  117. Speciale C.and Schwarcz R. (1990) Uptake of kynurenine into ratbrain slices. J. Neurochem. 54, 156–163.PubMedGoogle Scholar
  118. Speciale C., Ungerstedt U., and Schwartz R. (1989) Production of extracellular quinolinic acid in the striatum studied by microdialysis in unanesthetized rats. Neurosci. Lett. 104,345–350.PubMedGoogle Scholar
  119. Spector R. and Huntoon S. (1981) No effect of maternal niacin deficiency on niacin metabolism in newborn brain. Neurochem. Res. 6, 475–483.PubMedGoogle Scholar
  120. Spector R. and Kelly P. (1979) Niacin and niacinamide accumulation by rabbit brain slices and choroid plexus in vitro. J. Neurochem. 33, 291–298.PubMedGoogle Scholar
  121. Spector R. and Lorenzo A. V. (1975) Myo-inosital transport in the CNS. Am. J. Physiol. 228, 1510–1518.PubMedGoogle Scholar
  122. Spector R. (1979) Niacin and niacinamide transport in the CNS. In vivo studies. J. Neurochem. 33, 895–904.PubMedGoogle Scholar
  123. Stemberg S. S. and Philips F. S. (1958) 6-Aminonicotinamide and acute degenerative changes in the CNS. Science 127, 644–646.Google Scholar
  124. Stone T. W. and Perkins M. N. (1981) Quinolinic acid: A potent endogenous excitant at amino acid receptors in CNS. Eur. J. Phurmacol. 72, 411,412.Google Scholar
  125. Strandell E., Eizirik D. L., and Sandler S. (1989) Survival and B-cell function of mouse pancreatic islets maintained in culture after concomitant exposure to streptozotocin and nicotmamide. Exp. Clin. Endocrinol. 93, 219–224.PubMedGoogle Scholar
  126. Todd W. P., Carpenter B. K., and Schwartz R. (1989) Preparation of 4-halo-3-hydroxyanthranilates and demonstration of their inhibition of 3-hydroxyanthranilate oxygenase activity in rat and human brain tissue. Prep. Biochem. 19,155–165.PubMedGoogle Scholar
  127. Turski W. A., Gramsbergen J. B. P., Traitler H., and Schwartz R. (1989) Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine. J. Neurochem. 52, 1629–1636.PubMedGoogle Scholar
  128. Unna K. (1939) Studies on the toxicity and pharmacology of nicotinic acid. J. Phamtacol. Exp. Ther. 65, 95–103.Google Scholar
  129. Utter M. F. (1950) Mechanism of inhibition of anaerobic glycolysis of brain by sodium ions. J. Biol. Chem. 185, 499–517.PubMedGoogle Scholar
  130. Vezzani A., Stasi M. A., Wu H. Q., Castiglioni M., Weckermann B., and Samanin R. (1989) Studies on the potential neurotoxic and convulsant effects of increased blood levels of quinolinic acid in rats with altered blood-brain barrier permeability. Exp. Neural. 106, 90–98.Google Scholar
  131. Weil-Malherbe H. and Bone A. D. (1951) Studies on hexokinase. I. The hexokinase activity of rat brain extracts. Biochem. J. 49,339–347.PubMedGoogle Scholar
  132. Willing F., Neuhoff V., and Herken H. (1964) Der Austausch von 3-acetylpyridin gegen nicotinsaureamid in den pyridinnucleotiden verschiedener hirnregionen. Naunyn-Schmied. Arch. Pharmacol. 247, 254–266.Google Scholar
  133. Windmueller H. G. and Kaplan N. O. (1962) Solubilization and purification of diphosphopyridine nucleotidase from pig brain. Biochim. Biophys. Acta 56, 388–391.PubMedGoogle Scholar
  134. Winer A. D. (1960) Fluorescent studies of ox-brain lactic and malic dehy-drogenase. Biochem. J. 76, 5p–6p.Google Scholar
  135. Wolf A. and Cowen D. (1959) Pathological changes in the CNS produced by 6-aminonicotinamide. Bull. N.Y. Acad. Med. 35, 814–817.PubMedGoogle Scholar
  136. Woolley D. W. (1952) A Study of Antimetabolites. Chapman and Hall, LondonGoogle Scholar

Copyright information

© The Humana Press Inc 1992

Authors and Affiliations

  • Frederick C. Kauffman
    • 1
  1. 1.Laboratory for Cellular and Biochemical ToxicologyRutgers University College of PharmacyPiscataway

Personalised recommendations