Summary
5,6-dihydroxytryptamine (5,6-DHT) has been found to induce a substantial degree of “chemical degeneration” of indoleamine containing nerve terminals in the rat brain following a single intraventricular injection of 75 μg 5,6-DHT per animal. The disintegration of varicose terminal portions of serotonin containing neurons is reflected
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by a loss of yellow fluorescent varicosities in certain defined parts of the rat CNS, despite a mild inhibition of the serotonin catabolizing enzyme monoamine oxidase with nialamide in the pretreated animals,
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by a significant drop of the chemically measurable 5-hydroxytryptamine content in nearly all parts of the rat brain and spinal cord,
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by the appearance of highly, orange or brownish fluorescent axons provided with numerous unusually large, distorted and intensely fluorescent swellings (“droplets”), resembling proximal stumps of mechanically severed indoleamine containing axons,
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a temporary increase in the amount of indoleamine fluorophores stored in some neuronal pericarya, and
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the electron microscopical demonstration of degenerating synaptic swellings of unmyelinated axons at all sites investigated.
The selectivity of the effect of 5,6-DHT on indoleamine neurons is indicated by the absence of similar signs of injury in catecholamine containing neurons of the rat CNS.
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References
Anden, N. E., Carlsson, A., Häggendal, J.: Adrenergic mechanisms. Ann. Rev. Pharmacol. 9, 119–134 (1969).
— Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurons to the telencephalon and diencephalon. Acta physiol. scand. 67, 313–326 (1966).
Baumgarten, H. G.: Vorkommen und Verteilung adrenerger Nervenfasern im Darm der Schleie (Tinca vulgaris Cuv.). Z. Zellforsch. 76, 248–259 (1967).
-- Uptake and distribution of false transmitters and their precursors in adrenergic sympathetic nerves of the guinea-pig vas deferens, In: Morphological aspects of andrology, eds. A. F. Holstein, E. Horstmann, p. 141–146. Fortschr. Androl. I (1970).
-- Biogenic monoamines in the cyclostome and lower vertebrate brain. Progr. Histochem. Cytochem., in press (1972).
-- Björklund, A., Holstein, A. F., Nobin, A.: Chemical degeneration of serotonin terminals in rat brain: An ultrastructural study. In preparation (1972).
-- -- -- Nobin, A.: Organization and ultrastructural identification of the catecholamine nerve terminals in the neural lobe and pars intermedia of the rat pituitary. Z. Zellforsch. 1972, in press.
-- -- Lachenmayer, L., Nobin, A., Stenevi, U.: Long lasting selective depletion of brain serotonin by 5,6-dihydroxytryptamine. Acta physiol. scand., Suppl. 373 (1971).
— Braak, H.: Catecholamine im Gehirn der Eidechse. (Lacerta viridis und Lacerta muralis). Z. Zellforsch. 86, 574–602 (1968).
-- Evetts, K. D., Holman, B., Iversen, L. L., Vogt, M., Wilson, G.: Effects of 5,6-dihydroxytryptamine on monoaminergic neurons in the central nervous system of the rat. J. Neurochem. 1972, in press.
-- Göthert, M., Holstein, A. F., Schlossberger, H. G.: Chemical sympathectomy by means of 5,6-dihydroxytryptamine. Z. Zellforsch., in press, 1972.
— Owman, Ch.: Auerbach's plexus of mammals and man: Electron microscopic indentification of three different types of neuronal processes in myenteric ganglia of the large intestine from rhesus monkeys, guinea-pigs and man. Z. Zellforsch. 106, 376–397 (1970).
-- Lachenmayer, L.: Chemically induced degeneration of indoleamine containing nerve terminals in rat brain. Brain Res. in press (1972).
Bell, L. J., Iversen, L. L., Uretsky, N. J.: Time course of effects of 6-hydroxydopamine on catecholamine containing neurons in rat hypothalamus and striatum. Brit. J. Pharmacol. 40, 790–799 (1970).
Bertler, A.: Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta physiol. scand. 51, 75–83 (1961).
— Carlsson, A., Rosengren, E., Waldeck, B.: A method for the fluorimetric determination of adrenaline, noradrenaline and dopamine in tissues. Kgl. fysiogr. Sällsk. Lund Förh. 28, 121–123 (1958).
Björklund, A.: Monoamine containing fibres in the pituitary neuro-intermediate lobe of the pig and rat. Z. Zellforsch. 89, 573–589 (1968).
— Ehinger, B., Falck, B.: A method for differentiating dopamine from noradrenaline in tissues by microspectrofluorometry. J. Histochem. Cytochem. 16, 263–270 (1968).
— Falck, B., Hromek, F., Owman, Ch., West, K. A.: Identification and terminal distribution of the tubero-hypophyseal monoamine fibre systems in the rat by means of stereotaxic and microspectrofluorimetric techniques. Brain Res. 17, 1–23 (1970).
— Falck, B. Stenevi, U.: On the possible existence of a new intraneuronal monoamine in the spinal cord of the rat. J. Pharmacol. exp. Ther. 175, 525–532 (1970).
Björklund, A., Falck, B., Stenevi, U.: Classification of monoamine neurons in the rat mesencephalon: Distribution of a new monoamine neurone system. Brain Res. 32, 1–17 (1971).
-- -- -- Microspectrofluorimetric characterization of monoamines in the central nervous system: Evidence for a new neuronal monoamine-like compound. Progr. Brain Res., in press.
Braak, H.: Biogene Amine im Gehirn vom Frosch (Rana esculenta). Z. Zellforsch. 106, 269–308 (1970).
— Baumgarten, H. G.: 5-Hydroxytryptamin im Zentralnervensystem vom Goldfisch (Carassius auratus). Z. Zellforsch. 81, 416–432 (1967).
— Falck, B.: 5-Hydroxytryptamin im Gehirn der Eidechse (Lacerta viridis und Lacerta muralis). Z. Zellforsch. 90, 161–185 (1968).
Breese, G. R., Traylor, T. D.: Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: evidence for selective degeneration of catecholamine neurons. J. Pharmacol. exp. Ther. 174, 413–420 (1970).
Corrodi, H., Hillarp, N. A., Jonsson, G.: Fluorescence methods for the histochemical demonstration of monoamines.III. Sodium borohydride reduction of the fluorescent compounds as a specificity test. J. Histochem. Cytochem. 12, 582–586 (1964).
— Jonsson, G.: The formaldehyde fluorescence method for the histochemical demonstration of biogenic monoamines. A review on the methodology. J. Histochem. Cytochem. 15, 65–78 (1967).
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232 (1964).
-- -- II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta physiol. scand. 64, Suppl. 247 (1965).
— Häggendal, J.: Axonal transport of amine storage granules in sympathetic adrenergic neurons. In: Biochemistry of simple neuronal models, ed. by E. Costa, E. Giacobini, p. 65–93. New York: Raven Press 1970.
Falck, B., Owman, Ch.: A detailed methodological description of the fluorescence method for the cellular demonstration of biogenic monoamines. Acta Univ. Lund. II, No 7, 1–23 (1965).
Fink, R. P., Heimer, L.: Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res. 4, 369–374 (1967).
Furness, J. B., Campbell, G. R., Gillard, S. M., Malmfors, T., Cobb, J. L. S., Burnstock, G.: Cellular studies of sympathetic degeneration produced by 6-hydroxydopamine in the vas deferens. J. Pharmacol. exp. Ther. 174, 111–122 (1970).
Fuxe, K., Hökfelt, T., Ungerstedt, U.: Localization of indolealkylamines in CNS. Advanc. Pharmacol. 6, 235–251 (1968).
— Ungerstedt, U.: Histochemical studies on the distribution of catecholamines and 5-hydroxytryptamine after intraventricular injections. Histochemie 13, 16–28 (1968).
Häggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand. 59, 242–254 (1963).
Haeusler, G., Haefely, W., Thoenen, H.: Chemical sympathectomy of the cat with 6-hydroxydopamine. J. Pharmacol. exp. Ther. 170, 50–61 (1969)
Himwich, H. E., Alpers, H. S.: Psychopharmacology. Ann. Rev. Pharmacol. 10, 313–334 (1970).
Iversen, L. L., Uretsky, N. J.: Regional effects of 6-hydroxydopamine on catecholamine containing neurons in rat brain and spinal cord. Brain Res. 24, 364–367 (1970).
Jonsson, G., Sachs, Ch.: Effects of 6-hydroxydopamine on the uptake and storage of noradrenaline in sympathetic adrenergic neurons. Europ. J. Pharmacol. 9, 141–155 (1970).
Kapeller, K., Mayor, D.: Accumulation of noradrenaline (H3) in constricted sympathetic nerves as studied by fluorescence and electron microscopy. Proc. roy. Soc. B 167, 282–292 (1967).
Noble, E. P., Wurtman, R. J., Axelrod, J.: A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain. Life Sci. 6, 281–291 (1967).
Praag, H. M., van: Indoleamines and the central nervous system. A sounding of their clinical significance. Psychiat. Neurol. Neurochir. (Amst.) 73, 9–36 (1970).
Ritzén, M.: Quantitative fluorescence microspectrophotometry of 5-hydroxytryptamine-formaldehyde products in models and in mast cells. Exp. Cell Res. 45, 178–194 (1966).
Schlossberger, H. G., Kuch, H.: Synthese des 5,6-Dihydroxytryptamins. Chem. Ber. 93, 1318–1323 (1960).
Stenevi, U.: Sprouting and plasticity of central monoamine neurons with microspectrofluorometric characterization of their intraneuronal fluorophores. Comm. Departm. Anat. Univ. Lund, No 2, 1971.
Sulser, F., Sanders-Bush, E.: Effect of drugs on amines in the CNS. Ann. Rev. Pharmacol. 11, 209–230 (1971).
Thoenen, H.: Biochemical alterations induced by 6-hydroxydopamine in peripheral adrenergic neurons. In: 6-hydroxydopamine and catecholamine neurons, ed. T. Malmfors, H. Thoenen, p. 75–85. Amsterdam-London: North-Holland Publ. Co. 1971.
Tranzer, J. P., Thoenen, H.: Ultramorphologische Veränderungen der sympathischen Nervenendigungen der Katze nach Vorbehandlung mit 5- und 6-Hydroxydopamin. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 257, 343–344 (1967).
Ungerstedt, U.: I. Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. scand., Suppl. 367 (1971).
Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on catecholamine containing neurons in the rat brain. J. Neurochem. 17, 269–278 (1970).
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Supported by grants from the Deutsche Forschungsgemeinschaft.
Supported by the Joachim-Jungius-Gesellschaft zur Förderung der Wissenschaften, Hamburg.
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Baumgarten, H.G., Lachenmayer, L. & Schlossberger, H.G. Evidence for a degeneration of indoleamine containing nerve terminals in rat brain, induced by 5,6-dihydroxytryptamine. Z.Zellforsch 125, 553–569 (1972). https://doi.org/10.1007/BF00306659
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DOI: https://doi.org/10.1007/BF00306659