Summary
The nicotinamide antagonist 6-aminonicotinamide (6-AN) administered to rats prior to the second postnatal week drastically affected their motoric activity by producing consecutive reversible hypo- and hypermotoric stages. To obtain information on the validity of the putative link of correlated changes in brain RNA synthesis and motoric activity, neuronal and nonastrocytic glial cerebral and cerebellar in vitro RNA synthesis was determined during the hypo- and hypermotoric stages induced by in vivo administration of 6-AN given on the 7th day of a rat's life.
Significant changes were apparent in the rate of neuronal cerebral and cerebellar RNA synthesis coinciding with the different phases of motor activity. However, only the changes in neuronal cerebral RNA synthesis were directly proportional to the changing pattern of motor activity. Measurement of the total number of RNA initiation sites present in neuronal cerebral chromatin, which was isolated during the phase of reduced and elevated muscular activity, revealed that the drug-induced changes in neuronal cerebral RNA synthesis could be directly attributed to a genetically repressed or activated state of the corresponding neuronal chromatin fraction. Nevertheless, although there was evidence suggesting a connection between changes in neuronal cerebral RNA synthesis and corresponding changes in muscular activity it was difficult to deduce any direct relationship between parameters owing to the absence of a convincing biological assay for assessing the role of RNA in motor function.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Austoker, J., Cox, D., Mathias, A.P.: Fractionation of nuclei from brain by zonal centrifugation and a study of the ribonucleic acid polymerase activity in the various classes of nuclei. Biochem. J. 129, 1139–1155 (1972)
Banks-Schlegel, S.P., Johnson, T.C.: RNA metabolism in isolated mouse brain nuclei during early postnatal development. J. Neurochem. 24, 947–952 (1975)
Bielicki, L., Krieglstein, J.: Inhibition of glucose phosphorylation in rat brain by thiopental. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 25–29 (1976)
Brown, J.R.: RNA synthesis in isolated brain nuclei after administration of d-lysergic acid diethylamide (LSD) in vivo. Proc. Natl. Acad. Sci. (Wash.) 72, 837–839 (1975)
Burton, K.: A study of the conditions and mechanisms of the diphenylamine reaction for colorimetric estimation of DNA. Biochem. J. 62, 315–323 (1956)
Cedar, H., Felsenfeld, G.: Transcription of chromatin in vitro. J. Mol. Biol. 77, 237–254 (1973)
Chamberlain, M.J., Ring, J.: Studies of the binding of E. coli RNA polymerase to DNA. Biol. 70, 221–237 (1972)
Cupello, A., Hydén, H.: Alteration of the pattern of hippocampal nerve cell RNA labelling during training in rats. Brain Res. 114, 453–460 (1976)
Cupello, A., Hydén, H.: Studies on RNA metabolism in the nerve cells of hippocampus during training in rats. Exp. Brain Res. 31, 143–152 (1978)
Dewar, A.J., Shields, P.J.: The relationship between electrical stimulation and RNA metabolism in rat brain. Brain Res. 38, 182–186 (1972)
Desphande, S.S., Albuquerque, E.X., Kauffman, F.C., Guth, L.: 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 (1978)
Edström, J.-E., Grampp, W.: Nervous activity and metabolism of ribonucleic acids in the crustacean stretch receptor neuron. J. Neurochem. 12, 735–741 (1965)
Ermini, M., Kunzle, C.C.: The chromatin repeat length of cortical neurons shortens during early postnatal development. FEBS-Lett. 90, 167–172 (1978)
Friede, R.L., Fleming, L.M., Knoller, M.: A comparative mapping of enzymes involved in hexosemonophosphate shunt and citric acid cycle in the brain. J. Neurochem. 10, 263–277 (1963)
Genazzani, E., Carlo, R. di: Interference of neurologically active drugs with metabolism of RNA in brain. In: Central nervous system, Genazzani, E., Herken, H. (eds.), pp. 217–222. Berlin, Heidelberg, New York: Springer 1974
Giuffrida, M.A., Cox, D., Mathias, A.P.: RNA polymerase activity in various regions of rat brain during postnatal development. J. Neurochem. 24, 749–755 (1975)
Glees, P.: Neuroglia, Morphology, and Function. Oxford: Blackwell 1955
Herken, H., Lange, K., Kolbe, H.: Brain disorder induced by pharmacological blockade of the pentose phosphate pathway. Biochem. Biophys. Res. Commun. 36, 93–100 (1969)
Herken, H., Lange, K.: Blocking of pentose phosphate pathway in the brain of rats by 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmak. Exp. Path. 263, 496–499 (1969)
Herken, H., Lange, K., Kolbe, H., Keller, K.: Antimetabolic action on the pentose phosphate pathway in the central nervous system induced by 6-aminonicotinamide. In: Central nervous system studies on metabolic regulation and function, Genazzoni, E., Herken, H. (eds.), pp. 41–54. Berlin, Heidelberg, New York: Springer 1974
Hydén, H., Egyhazi, E.: The effect of tranylcypromine on synthesis of macromolecules an enzyme activities in neurons and glia. Neurology 18, 732–736 (1968)
Jarlstedt, J., Hamberger, A.: Patterns and labelling characteristics in neuronal and glial RNA. Neurochem. 18, 921–930 (1971)
Johnson, W.J., Coll, J.D.: 6-Aminonicotinamide a potent nicotinamide antagonist. Science 122, 834–842 (1955)
Kalimi, M., Tsai, M.-J., Clark, J.H., O'Malley, B.W.: Effects of estrogen on gene expression in the chick oviduct. J. Biol. Chem. 251, 516–523 (1976)
Kato, T., Kurokawa, M.: Studies on ribonucleic acid and homopolyribonucleotide formation in neuronal, glial and liver nuclei. Biochem. J. 116, 599–609 (1970)
Kauffman, F.C., Johnson, E.G.: Cerebral energy reserves and glycolysis in neural tissue of 6-aminonicotinamide-treated mice. J. Neurobiol. 5, 379–392 (1974)
Keller, K., Kolbe, H., Lange, K., Herken, H.: Behaviour of the glycolytic system of rat brain and kidney in vivo after inhibition of the glucose-phosphate isomerase. II. Substrate concentrations under the influence of ischemia, 6-aminonicotinamide, and 2-deoxyglucose. Hoppe-Seylers Z. Physiol. Chem. 353, 1389–1400 (1972)
Kogan, A.B., Zaguskin, S.L.: Correlated changes in ribonucleic acid and electrical activity for crayfish single stretch receptor neurons during excitability and inhibition. Fed. Proc. 24, T 191–195 (1965)
Köhler, E., Barrach, H.-J., Neubert, D.: Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analogue of NADP. FEBS Lett. 6, 225–228 (1970)
Krieglstein, J., Stock, R.: Decreased glycolytic flux rate in the isolated perfused rat brain after pretreatment with 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 323–327 (1975)
Krylov, O.A., Danylova, R.A., Tongur, V.S.: On the participation of RNA in reflectoral activity of white mice. Life Sci. 4, 1313–1317 (1965)
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)
Moore, B.W.: Proteins of the Nervous System, Schneider, D.J., (ed.), pp. 1–12. New York: Raven Press 1973
Nurnberger, J.I., Gordon, M.W.: Progress in neurobiology, Waelsch, M. (ed.), Vol. 2, pp. 100–138. New York: Harper and Row 1957
Orrego, F.: Synthesis of RNA in normal and electrically stimulated brain slices in vitro. J. Neurochem. 14, 851–858 (1967)
Pomerai, D., de Chesterton, C.J., Butterworth, P.H.W.: Preparation of chromatin. Eur. J. Biochem. 46, 461–471 (1974)
Prives, C., Quastel, J.H.: Effects of cerebral stimulation on biosynthesis of nucleotides and RNA in brain slices in vitro. Biochim. Biophys. Acta 182, 285–294 (1969)
Rose, S.P.R.: Neurons and glia seperation techniques and biochemical interrelationships. In: Handbook of neurochemistry, Lajtha, A. (ed.) Vol. 2, pp. 183–193. New York: Plenum Press 1969
Sarkander, H.-I., Dulce, H.-J.: Studies on the regulation of RNA synthesis in neuronal and glial nuclei isolated from rat brain. Exp. Brain Res. 31, 317–327 (1978)
Sarkander, H.-L., Knoll-Köhler, E., Cervos-Navarro, J.: Repression of glial RNA transcription during the development of 6-aminonicotinamide (6-AN)-induced acute gliopathy. J. Pharmacol. Exp. Ther. 205, 503–514 (1978)
Sarkander, H.-I., Uthoff, C.G.: Comparison of the number of RNA initiation sites in rat brain fractions enriched in neuronal or glial nuclei. FEBS Lett. 71, 53–56 (1976)
Schneider, H., Coper, H.: Morphologische Befunde am Zentralnervensystem nach Vergiftung mit Antimetaboliten des Nicotinamids (6-Aminonicotin-säureamid and 3-Acetylpyridin) und einem Cholinderivat (5-Nitro-8-hydroxychinolin). Arch. Psychiat. Z. Gesamt. Neurol. 211, 138–154 (1968)
Schneider, H., Cervos-Navarro, J.: Acute gliopathy in spinal cord and brain stem induced by 6-aminonicotinamide. Acta Neuropathol. (Berlin) 27, 11–23 (1974)
Smythies, J.R.: Receptors: possible molecular complexes involved in receptor sites and transmitter storage mechanisms. In: Handbook of neurochemistry, Lajtha, A. (ed.), Vol. 5, pp. 631–643. New York: Plenum Press 1971
Sternberg, S.S., Philips, F.S.: 6-Aminonicotinamide and acute degenerative changes in the central nervous system. Science 127, 642–644 (1958)
Thomas, J.O., Thompson, R.J.: Variation in chromatin structure in two cell types from the same tissue: a short DNA repeat length in cerebral cortex neurons. Cell 10, 633–640 (1977)
Tsai, M.J., Towle, H.C., Harris, S.E., O'Malley, B.W.: Effect of estrogen on gene expression in the chick oviduct. J. Biol. Chem. 251, 1960–1968 (1976)
Volpe, P., Guiditta, A.: Kinetics of RNA labelling in fractions enriched with neuroglia and neurons. Nature 216, 154 (1967)
Wolf, A., Cowen, D.: Pathological changes in the central nervous system produced by 6-aminonicotinamide. Bull. NY Acad. Med. 35, 814–817 (1959)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Knoll-Köhler, E., Wojnorowicz, F. & Sarkander, H.J. 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 (1980). https://doi.org/10.1007/BF00236738
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00236738