Skip to main content
Log in

Alteration of acetylcholine synthesis in mouse brain cortex in mild hypoxie hypoxia

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Acetylcholine synthesis in four brain regions (cerebral neocortex, hippocampus, septum and striatum) of the mouse during mild hypoxic hypoxia was measured by using [U-14C]glucose and [2H4] choline. At the same time, concentrations of norepinephrine and dopamine in four brain regions (cerebral neocortex, hippocampus, striatum and hypothalamus) were also estimated.

During 12% O2 hypoxia, concentrations of acetylcholine in the striatum were significantly decreased (P<0.05), whereas [2H4] acetylcholine, lactate and glucose did not alter in any regions studied. During 12% O2 hypoxia, concentrations of choline and [2H4]choline were significantly increased in all regions examined (P<0.05), except the [2H4]choline in the striatum. Radioactivity (dpm/100 mg protein) and specific activity (dpm/nmol) of acetylcholine were significantly decreased in the cerebral neocortex, hippocampus and septum (P<0.01) during 12% O2 hypoxia. A particularly marked decrease was found in the hippocampus, strongly suggesting that cholinergic terminals are particularly sensitive to hypoxia. In addition, these data also suggest that the acetylcholine synthesis from glucose might be more sensitive to hypoxia than that from choline.

During 12% O2g hypoxia, concentrations of catecholamine did not alter in any regions examined, whereas during 9% O2 hypoxia dopamine was significantly decreased in the cerebral neocortex and hippocampus (P<0.05).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Benzi, G., Arrigioni, E., Dagani, F., Pastoris, O., Villa, R. F., Agnoli, A. Cerebral energy state during or after hypoxia and complete or incomplete ischemia. J. appl. Physiol.45, 312–319 (1978).

    Google Scholar 

  • Bier, D. M., Sherman, W. R., Holland, W. H., Kipnis, D. M.: Thein vivo measurement of alanine and glucose turnover with deuterium labelled metabolites. In: Proceedings of the First International Conference on Stable Isotopes in Chemistry, Biology and Medicine (Klein, P. D., Peterson, S. V., eds.), pp. 397–403. Springfield, Va.: 1973.

  • Blank, L. C., Casa, S., Isernhagen, R., Meyerson, L. R., Wassil, D., Wong, P., Modak, A. T., Stavinoha, W. B. Level of norepinephrine and dopamine in mouse brain regions following microwave inactivation. Rapid postmortem degradation of striatal dopamine in decapitated animals. J. Neurochem.33, 213–219 (1979).

    Google Scholar 

  • Browning, E. T. Acetylcholine synthesis: Substrate availability and the synthetic reaction. In: Biology of Cholinergic Function (Goldberg, A. M., Hanin, I., eds.), pp. 187–201. New York: Raven Press. 1976.

    Google Scholar 

  • Buxton, P. H. Neuropathological findings in experimental hypoxia. Proc. R. Soc. Med.53, 638–684 (1960).

    Google Scholar 

  • Carlsson, A., Lindqvtst, M., Keh, W. Post-mortal accumulation of 3-methoxytyramine in brain. Naunyn-Schmiedeberg's Arch. Exp. Path. Pharmac.284, 365–372 (1974).

    Google Scholar 

  • Cheney, D. L., Racagni, R., Costa, E. Distribution of acetylcholine and choline acetyltransferase in specific nuclei and tracts of rat brain. In: Biology of Cholinergic Function (Goldberg, A. M., Hanin, I., eds.), pp. 655–659. New York: Raven Press. 1976.

    Google Scholar 

  • Davis, J. N., Carlsson, A. The effect of hypoxia on monoamine synthesis, levels and metabolism in rat brain. J. Neurochem.21, 783–790 (1973).

    Google Scholar 

  • Davis, J. N. Brain tyrosine hydroxylation: Alteration of oxygen affinityin vivo by immobilization or electroshock in the rat. J. Neurochem.27, 211–215 (1976).

    Google Scholar 

  • Davis, K. L., Yamamura, H. I. Cholinergic underactivity in human memory disorders. Life Sci.23, 1729–1734 (1978).

    Google Scholar 

  • Debijadji, R., Perovic, L., Varagii, V., Stosic, N. Effect of hypoxic hypoxia on the catecholamine content and some cytochemical changes in the hypothalamus of the cat. Aerospace Med.40, 495–499 (1969).

    Google Scholar 

  • Ernsting, J. Effect of anoxia on the central nervous system. In: A Textbook of Aviation Physiology (Gillies, J. A., ed.), pp. 270–289. New York: Pergamon Press. 1965.

    Google Scholar 

  • Eksborg, S., Persson, B. A. Photometric determination of acetylcholine in rat brain after selective isolation by ion pair extraction and micro column separation. Acta Pharm. Suecica8, 205–216 (1971).

    Google Scholar 

  • Fonnum, F. Topographical and subcellular localization of choline acetyltransferase in rat hippocampal region. J. Neurochem.17, 1029–1037 (1970).

    Google Scholar 

  • Freeman, J. J., Choi, R. L., Jenden, D. J. Plasma choline: its turnover and exchange with brain choline. J. Neurochem.24, 729–734 (1975).

    Google Scholar 

  • Galli, C. L., Cattabeni, F., Eros, T., Spano, P. F., Algeri, S., Giulio, D. A., Groppetti, A. A mass fragmentographic assay of 3-methoxytyramine in rat brain. J. Neurochem.27, 795–798 (1976).

    Google Scholar 

  • Gibson, G. E., Shimada, M., Blass, J. P. Alterations in acetylcholine synthesis and cyclic nucleotides in mild cerebral hypoxia. J. Neurochem.31, 757–760 (1978).

    Google Scholar 

  • Gornall, A. G., Bardawill, C. J., David, M. M. Determination of serum proteins of the biuret reaction. J. biol. Chem.177, 751–766 (1949).

    Google Scholar 

  • Hanin, I., Massarelli, R., Costa, E. Acetylcholine concentrations in rat brain: Diurnal Oscillation. Science170, 341–342 (1970).

    Google Scholar 

  • Hebb, C. O., Krnjevic, K., Silver, A. Effect of undercutting on the acetylcholinesterase and choline acetyltransferase activity in the cat's cerebral cortex. Nature198, 692 (1963).

    Google Scholar 

  • Hedner, T., Lundborg, P., Engel, J. Effect of hypoxia on monoamine synthesis in brains of developing rats. Biol. Neonate31, 122–126 (1977 a).

    Google Scholar 

  • Hedner, T., Lundborg, P., Engel, J. Effect of hypoxia on monoamine synthesis in brains of developing rats. II. Different length of exposure. Biol. Neonate32, 229–236 (1977 b).

    Google Scholar 

  • Hedner, T., Lundborg, P., Engel, J. Effect of hypoxia on monoamine synthesis in brains of developing rats. III. Various O2 levels. Biol. Neonate34, 55–60 (1978).

    Google Scholar 

  • Hedner, T., Lundborg, P. Regional changes in monoamine synthesis in the developing rat during hypoxia. Acta Physiol. Scand.106, 139–143 (1979).

    Google Scholar 

  • Hurwitz, D. A., Robinson, S. M., Barofsky, I. Behavioral decrements and brain catecholamine changes in rat exposed to hypobaric hypoxia. Psychopharmacologia (Berl.)19, 26–33 (1971).

    Google Scholar 

  • Jenden, D. J., Roch, M., Booth, R. A. Simultaneous measurement of endogenous and deutrium-labeled tracer variants of dioline and acetylcholine in subpicomole quantities by gas chromatography/mass spectrometry. Anal. Biochem.55, 438–448 (1973).

    Google Scholar 

  • Karlen, B., Lundgren, G., Nordgren, I., Holmstedt, B. Ion-pair extraction and gas-phase analysis of acetylcholine and chorine. In: Choline and Acetylcholine: Handbook of Chemical Assay Methods (Hanin, I., ed.), pp. 163–179. New York: Raven Press. 1974.

    Google Scholar 

  • Karlen, B., Lundgren, G., Lundin, J., Holmstedt, B. Effects of oxotremorine on synthesis of acetylcholine in striatum and whole brain of mice killed by various techniques. Life Sci.20, 1651–1656 (1977).

    Google Scholar 

  • Karoum, F., Gillin, J. C., Wyatt, R. J., Costa, E. Mass fragmentography of nanogram quantities of biogenic amine metabolites in human cerebrospinal fluid and whole rat brain. Medical Mass Spectrometry2, 183 to 189 (1975).

    Google Scholar 

  • Kubar, M. J., Setby, V. H., Roth, R. H., Aghajanian, G. K. Choline: Selective accumulation by central cholinergic neurons. J. Neurochem.20, 581–593 (1973).

    Google Scholar 

  • Kubar, M. J. The anatomy of cholinergic neurons. In: Biology of Cholinergic Function (Goldberg, A. M., Hanin, I., eds.), pp. 3–7. New York: Raven Press. 1976.

    Google Scholar 

  • Lowry, O. H., Passoneau, J. V. A Flexible System of Enzymatic Analysis, pp. 199–201. New York: Academic Press. 1972.

    Google Scholar 

  • Malthe-Sorenssen, D., Wood, P. L., Cheney, D. L., Costa, E. Modulation of the turnover rate of acetylcholine in rat brain by intraventricular injections of thyrotropin-releasing hormone, somatostatin, neurotensin and angiotensin II. J. Neurochem.31, 685–691 (1978).

    Google Scholar 

  • Mazzari, S., Finesso, M. Effect of ischemia on energy metabolism and catecholamine levels in the gerbil brainin vivo. Proc. Europ. Soc. Neurochem.1, 310 (1978).

    Google Scholar 

  • Meyerhoff, J. L., Kant, J. K., Lenox, R. H. Increase in dopamine in cerebral cortex and other regions of rat brain after microwave fixation: possible diffusion artifact. Brain Res.152, 161–169 (1978).

    Google Scholar 

  • Moroni, F., Cheney, D. L., Costa, E. Inhibition of acetylcholine turnover in rat hippocampus by intraseptal injection ofβ-endorphin and morphine. Naunyn-Schmiedeberg's Arch. Pharmacol.299, 149–153 (1977).

    Google Scholar 

  • Potempska, A., Gradkowska, M., Oderfeld-Nowak, B. Early changes in acetylcholine pools in the hippocampus of the rat brain after septal lesions. J. Neurochem.24, 787–789 (1975).

    Google Scholar 

  • Racagni, G., Bruno, F., Cattabeni, F., Maggi, A., Digilio, A. M., Groppetti, A. Interactions among dopamine, acetylcholine, and GABA in the nigro-striatal system. In: Interactions Between Putative Neurotransmitters (Garattini, S., Pujol, J. F., Samanin, R., eds.), pp. 61–72. New York: Raven Press. 1978.

    Google Scholar 

  • Richtarik, A., Hifl, H., Valdivia, E. Catecholamines in tissue of guinea pigs subjected to hypoxia. Arch. int. Pharmacodyn.159, 44–47 (1966).

    Google Scholar 

  • Roth, R. H., Bunny, B. S. Interaction of cholinergic neurons with other chemically defined neuronal systems in the CNS. In: Biology of Cholinergic Function (Goldberg, A. M., Hanin, I., eds.), pp. 379–394. New York: Raven Press. 1976.

    Google Scholar 

  • Schmidt, D. E., Speth, R. C., Welsch, F., Schmidt, M. J. The use of microwave radiation in the determination of acetylcholine in the rat brain. Brain Res.38, 377–389 (1972).

    Google Scholar 

  • Sethy, V. H., Roth, R. H., Kuhar, M. J., Van Woert, M. H. Choline and acetylcholine: regional distribution and effect of degeneration of cholinergic nerve terminals in the rat hippocampus. Neuropharmacology12, 819–823 (1973).

    Google Scholar 

  • Sharpless, N. S., Brown, L. L. Use of microwave irradiation to prevent postmortem catecholamine metabolism: evidence for tissue disruption artifact in a discrete region of rat brain. Brain Res.140, 171–176 (1978).

    Google Scholar 

  • Shea, P. A., Aprison, M. H. The distribution of acetyl-CoA in specific areas of the CNS of the rat as measured by a modification of radioenzymatic assay for acetylcholine and choline. J. Neurochem.28, 51–58 (1977).

    Google Scholar 

  • Shimada, M., Iwata, K., Inoue, S., Otomo, S., Hino, O. Distribution of radioactive carbon from [U-14C] glucose in the adult mouse brainin vivo under normal and cyanide poisoned conditions. Acta Anat. Nippo.45, 175–184 (1970).

    Google Scholar 

  • Shimada, M., Kihara, T., Kurimoto, K., Watanabe, M. Incorporation of14C from [U-14C] glucose into free amino acids in mouse brain regions under cyanide intoxication. J. Neurochem.23, 379–384 (1974 a).

    Google Scholar 

  • Shimada, M., Kurimoto, K., Watanabe, M., Yoshida, Y. Effect of cyanide hypoxia on free amino acid metabolism in mouse brain. Jap. J. Hyg.28, 522–529 (1974 b).

    Google Scholar 

  • Shimada, M., Kihara, T., Watanabe, M., Kurimoto, K. Regional distribution of glucose in mouse brain. Neurochem. Res.2, 595–603 (1977).

    Google Scholar 

  • Siesjö, B. K., Johannsson, H., Ljunggren, B., Norberg, K. Brain Dysfunction in Metabolic Disorders, pp. 75–112. New York: Raven Press. 1974.

    Google Scholar 

  • Siesjö, B. K. Brain Energy Metabolism, pp. 398–452. Chichester-New York-Brisbane-Toronto: J. Wiley. 1978.

    Google Scholar 

  • Siesjö, B. K. Brain energy metabolism and catecholaminergic activity in hypoxia, hypercapnia and ischemia. J. Neural Transm., Suppl. 14, pp. 17–22. Wien-New York: Springer. 1978.

    Google Scholar 

  • Siesjö, B. K., Berntman, L., Rehncrona, S. Effect of hypoxia on blood flow and metabolic flux in the brain. In: Advances in Neurology (Fahrt, S., ed.), Vol. 26, pp. 267–283. New York: Raven Press. 1979.

    Google Scholar 

  • Sloviter, R. S., Connor, J. D. Postmortem stability of norepinephrine, dopamine, and serotonin in rat brain. J. Neurochem.28, 1129–1131 (1977).

    Google Scholar 

  • Stavinoha, W. B., Weintraub, S. T., Modak, A. T. The use of microwave heating to inactivate cholinesterase in the rat brain prior to analysis for acetylcholine. J. Neurochem.20, 361–371 (1973).

    Google Scholar 

  • Stavinoha, W. B., Weintraub, S. T., Modak, A. T. Regional concentrations of cholme and acetylcholine in the rat brain. J. Neurochem.23, 885–886 (1974).

    Google Scholar 

  • Stoner, H. B., Hunt, A. The effect of trauma on the activity of central noradrenergic neurones. Brain Res.112, 337–346 (1976).

    Google Scholar 

  • Spokes, E. G. S., Koch, D. J. Post-mortem stability of dopamine, glutamate decarboxylase and choline acetyltransferase in the brain under conditions stimulating the handling of human autopsy material. J. Neurochem.31, 381–383 (1978).

    Google Scholar 

  • Szerb, J. C., Hadhazy, P., Dudar, J. D. Release of [3H] acetylcholine from rat hippocampal slices: Effect of septal lesion and of graded concentrations of muscarinic agonists and antagonists. Brain Res.128, 285–291 (1977).

    Google Scholar 

  • Vogt, M. The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J. Physiol. (London)123, 451–481 (1954).

    Google Scholar 

  • Weintraub, S. T., Stavinoha, W. B., Pike, R. L., Morgan, W. W., Modak, A. T., Koslow, S. H., Blank, L. Evaluation of the necessity for rapid inactivation of brain enzymes prior to analysis of norepinephrine, dopamine and serotonin in the mouse. Life Sci.17, 1423–1428 (1975).

    Google Scholar 

  • Wiesel, F.-A., Sedvall, G. Post-mortal changes of dopamine and homovanillic acid levels in rat striatum as measured by mass fragmentography. Brain Res.65, 547–550 (1974).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimada, M. Alteration of acetylcholine synthesis in mouse brain cortex in mild hypoxie hypoxia. J. Neural Transmission 50, 233–245 (1981). https://doi.org/10.1007/BF01249145

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01249145

Keywords

Navigation