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Histochemical demonstration and mapping of 5-hydroxytryptamine- and catecholamine-containing neuron systems in the human fetal brain

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Summary

The distribution of monoamine neurons in the human fetal brain was studied by Falck-Hillarp fluorescence histochemistry. Catecholamine (CA)- and 5-hydroxytryptamine (5-HT)-neuron systems were found in the smallest brain studied, obtained from an embryo having a total length of 2.1 cm and a gestational age of 7 weeks. A marked proliferation and differentiation of the monoamine neuron systems took place between the 7th and 23rd week of gestation (the range covered in the present investigation) permitting a mapping of major cell groups, as well as several axon pathways and terminal innervation patterns.

The basic cytoarchitectonic features of the central monoamine neurons in human fetuses were strikingly similar to those of the fetal rat. Thus, a large complex of cell bodies was found in the developing substantia nigra area, in all probability the CA neurons of the nigro-striatal dopamine system. Axons projected towards the corpus striatum. Here, the putamen and, somewhat later, the caudate nucleus became richly innervated by CA nerve terminals. Small clusters of CA nerve cells were found in the hypothalamus, e. g. in the ventral periventricular area.

5-hydroxytryptamine nerve cell bodies were distributed throughout the raphe areas from the medulla oblongata to the mesencephalon forming several well delineated groups, e.g. a large group in the area of nuc. raphe dorsalis. 5-HT axons projected caudally in the ventral parts of the medulla oblongata and into the spinal cord and rostrally through the mesencephalon and into the forebrain.

CA cell bodies were also found in several large complexes of the medulla oblongata and pons, where such cell bodies are of the noradrenaline type in animals. The principal locus coeruleus consisted of densely packed fluorescent cells and several loosely packed groups extended laterally, medially, dorsally and rostrally from this area. Several axon bundles ascended dorsally from this complex. Ventrally and dorsally located CA cell groups were found in the medulla oblongata, and green fluorescent axons descended into the spinal cord.

Varicose nerve terminals of the CA type were found, e.g. in the spinal cord, around the third ventricle and, using brain smears, also in the developing cerebral and cerebellar cortices.

There seemed to be an outflow of CA axons in ventral nerve roots of cranial and spinal nerves. The developing pineal gland showed scattered 5-HT-containing parenchymal cells. Area postrema contained a number of strongly fluorescent CA cells and some weaker fluorescent 5-HT cells.

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References

  • Andén, N.-E., Carlsson, A., Dahlström, A., Fuxe, K., Hillarp, N.-Å., Larsson, K.: Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci. 3, 523–530 (1964).

    Google Scholar 

  • Andén, N.-E., 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).

    Google Scholar 

  • Arey, L. B.: Developmental anatomy, 6th. ed. Philadelphia and London: Saunders 1954.

    Google Scholar 

  • Battista, A., Fuxe, K., Goldstein, M., Ogawa, M.: Mapping of central monoamine neurons in the monkey. Experientia (Basel) 28, 688–690 (1972).

    Google Scholar 

  • Bertler, A.: Occurrence and localization of catecholamines in the human brain. Acta physiol. scand. 51, 97–107 (1961).

    Google Scholar 

  • Björklund, A., Owman, Ch., West, K. A.: Peripheral sympathetic innervation and serotonin cells in the habenular region of the rat brain. Z. Zellforsch. 127, 570–579 (1972).

    Google Scholar 

  • Carlsson, A., Falck, B., Fuxe, K., Hillarp, N.-Å.: Cellular localization of monoamines in the spinal cord. Acta physiol. scand. 60, 112–119 (1964).

    Google Scholar 

  • Carlsson, A., Falck, B., Hillarp, N.-Å.: Cellular localization of brain monoamines. Acta physiol. scand. 56, Suppl. 196, 1–28 (1962).

    Google Scholar 

  • Corrodi, H., Jonsson, G.: The formaldehyde fluorescence method for the histochemical demonstration of biogenic amines. A review on the methodology. J. Histochem. Cytochem. 15, 65–78 (1967).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Development of the uptake and storage of L-(3H) norepinephrine in the rat brain. J. Neurochem. 18, 2061–2075 (1971).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Tyrosine hydroxylase in rat brain: developmental characteristics. J. Neurochem. 19, 1117–1123 (1972a).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Dopamine-β-hydroxylase in the rat brain: developmental characteristics. J. Neurochem. 19, 449–459 (1972b).

    Google Scholar 

  • 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, 1–55 (1964).

    Google Scholar 

  • Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta physiol. scand. 64, Suppl. 247, 1–36 (1965a).

    Google Scholar 

  • Dahlström, A., Fuxe, K.: Evidence for the existence of an outflow of noradrenaline nerve fibers in the ventral roots of the rat spinal cord. Experientia (Basel) 21, 409 (1965b).

    Google Scholar 

  • De la Torre, J. C.: Catecholamines in the human diencephalon: A histochemical fluorescence study. Acta neuropath. (Berl.) 21, 165–168 (1972).

    Google Scholar 

  • Duvernoy, H., Koritké, J. G., Monnier, G., Jacquet, G.: Sur la vascularisation de l'area postrema et de la face posterieure du bulbe chez l'homme. Z. Anat. Entwickl.-Gesch. 138, 41–66 (1972).

    Google Scholar 

  • Ehringer, H., Hornykiewicz, O.: Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr. 38, 1236–1239 (1960).

    Google Scholar 

  • Falck, B., Hillarp, N.-Å., Thieme, G., Torp, A.: Fluorescence of catechol amines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10, 348–354 (1962).

    Google Scholar 

  • Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. III. The monoamine nerve terminal. Z. Zellforsch. 65, 573–596 (1965a).

    Google Scholar 

  • Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand. 64, Suppl. 247, 39–85 (1965b).

    Google Scholar 

  • Fuxe, K., Hökfelt, T.: Catecholamines in the hypothalamus and the pituitary gland. In: Frontiers in neuroendocrinology (W. F. Ganong and L. Martini, eds.), p. 47–96. London: Oxford Univ. Press, Inc. 1969.

    Google Scholar 

  • Fuxe, K., Hökfelt, T., Jonsson, G., Ungerstedt, U.: Fluorescence microscopy in neuroanatomy. In: Contemporary research methods in neuroanatomy (W. J. H. Nauta and S. O. E. Ebbesson, eds.), p. 275–314. Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Fuxe, K., Hökfelt, T., Olson, L., Ungerstedt, U.: Central monoaminergic pathways with emphasis on their relation to the so called “extrapyramidal motor system”. In: The pharmacology of the extrapyramidal system (O. Hornykiewicz, ed.). International encyclopedia of pharmacology and therapeutics. (1973) (in press).

  • Fuxe, K., Owman, Ch.: Cellular localization of monoamines in the area postrema of certain mammals. J. comp. Neurol. 125, 337–354 (1965).

    Google Scholar 

  • Hamberger, B.: Reserpine-resistant uptake of catecholamines in isolated tissues of the rat. A histochemical study. Acta physiol. scand., Suppl. 295, 1–56 (1967).

    Google Scholar 

  • Hamilton, W. J., Boyd, J. D., Mossman, H. W.: Human embryology. Cambridge: W. Heffer 1962.

    Google Scholar 

  • Hewitt, W.: The development of the human caudate and amygdaloid nuclei. J. Anat. (Lond.) 92, 377–382 (1958).

    Google Scholar 

  • Hewitt, W.: The development of the human internal capsule and lentiform nucleus. J. Anat. (Lond.) 95, 191–199 (1961).

    Google Scholar 

  • Hochstetter, F.: Beiträge zur Entwicklungsgeschichte des menschlichen Gehirns. Wien u. Leipzig: Deuticke 1919.

    Google Scholar 

  • Hochstetter, F.: Beiträge zur Entwicklungsgeschichte des menschlichen Gehirns. Wien u. Leipzig: Deuticke 1929.

    Google Scholar 

  • Hornykiewicz, O.: Dopamine (3-hydroxytyramine) and brain function. Pharmacol. Rev. 18, 925–964 (1966).

    Google Scholar 

  • Hyyppä, M.: Hypothalamic monoamines in human fetuses. Neuroendocrinology 9, 257–266 (1972).

    Google Scholar 

  • Jonsson, G.: Quantitation of fluorescence of biogenic monoamines. Progr. Histochem. Cytochem. 2, 299–334 (1971).

    Google Scholar 

  • Lidbrink, P., Jonsson, G.: Semiquantitative estimation of formaldehyde-induced fluorescence of noradrenaline in central noradrenaline nerve terminals. J. Histochem. Cytochem. 19, 747–757 (1971).

    Google Scholar 

  • Lloyd, K. G., Hornykiewicz, O.: Occurrence and distribution of aromatic l-amino acid (l-DOPA) decarboxylase in the human brain. J. Neurochem. 19, 1549–1559 (1972).

    Google Scholar 

  • Loizou, L.: The postnatal ontogeny of monoamine-containing neurones in the central nervous system of the albino rat. Brain Res. 40, 395–418 (1972).

    Google Scholar 

  • Maeda, T., Dresse, A.: Possibilités d'étude du trajet des fibres cérébrales monoaminergiques chez le rat nouvea-né. C. R. Soc. Biol. (Paris) 162, 1626–1629 (1968).

    Google Scholar 

  • Millard, S. A., Gál, E. M.: Hydroxylation and biogenic amine synthesis in the human fetus. J. Neurochem. 19, 2461–2464 (1972).

    Google Scholar 

  • Nygren, L.-G., Olson, L., Seiger, Å.: Regeneration of monoamine-containing axons in the developing and adult spinal cord of the rat following intraspinal 6-OH-dopamine injections or transections. Histochemie 28, 1–15 (1971).

    Google Scholar 

  • Nyström, B., Olson, L., Ungerstedt, U.: Noradrenaline nerve terminals in human cerebral cortices: First histochemical evidence. Science 176, 924–926 (1972).

    Google Scholar 

  • Olson, L., Fuxe, K.: On the projections from the locus coeruleus noradrenaline neurons: The cerebellar innervation. Brain Res. 28, 165–171 (1971).

    Google Scholar 

  • Olson, L., Fuxe, K.: Further mapping out of central noradrenaline neuron systems: Projections of the “subcoeruleus” area. Brain Res. 43, 289–295 (1972).

    Google Scholar 

  • Olson, L., Hamberger, B., Jonsson, G., Malmfors, T.: Combined fluorescence histochemistry and 3H-noradrenaline measurements of adrenergic nerves. Histochemie 15, 38–45 (1968).

    Google Scholar 

  • Olson, L., Nyström, B., Seiger, Å.: Monoamine fluorescence histochemistry of human postmortem brain. Brain Res. (1973) (in press).

  • Olson, L., Seiger, Å.: Early prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations. Z. Anat. Entwickl.-Gesch. 137, 301–316 (1972).

    Google Scholar 

  • Olson, L., Seiger, Å., Fuxe, K.: Heterogeneity of striatal and limbic dopamine innervation: Highly fluorescent islands in developing and adult rats. Brain Res. 44, 283–288 (1972).

    Google Scholar 

  • Olson, L., Ungerstedt, U.: A simple high capacity freeze-drier for histochemical use. Histochemie 22, 8–19 (1970a).

    Google Scholar 

  • Olson, L., Ungerstedt, U.: Monoamine fluorescence in CNS smears: sensitive and rapid visualization of nerve terminals without freeze-drying. Brain Res. 17, 343–347 (1970b).

    Google Scholar 

  • O'Rahilly, R., Gardner, E.: The timing and sequence of events in the development of the human nervous system during the embryonic period proper. Z. Anat. Entwickl.-Gesch. 134, 1–12 (1971).

    Google Scholar 

  • Poirier, L. J., Sourkes, T. L.: Influences of the substantia nigra on the catecholamine content of the striatum. Brain 88, 181–192 (1965).

    Google Scholar 

  • Rugh, R.: The Mouse: its reproduction and development. Minneapolis: Burgess Publishing Comp. 1968.

    Google Scholar 

  • Scheibel, M. E., Scheibel, A. B.: Anatomical basis of attention mechanisms in vertebrate brains. In: The neurosciences. A study program (G. C. Quarton, T. Melnechuk, F. O. Schmitt, eds.), p. 577–602. New York: Rockefeller University Press 1967.

    Google Scholar 

  • Seiger, Å., Olson, L.: Late prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations. (1973) (to be publ.).

  • Truex, R. C., Carpenter, M. B.: Human neuroanatomy. Baltimore: Waverly Press Inc. 1969.

    Google Scholar 

  • Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. scand., Suppl. 367, 1–48 (1971).

    Google Scholar 

  • Zeman, W., Innes, J. R. M.: Craigie's neuroanatomy of the rat. New York-London: Academic Press 1963.

    Google Scholar 

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Olson, L., Boréus, L.O. & Seiger, Å. Histochemical demonstration and mapping of 5-hydroxytryptamine- and catecholamine-containing neuron systems in the human fetal brain. Z. Anat. Entwickl. Gesch. 139, 259–282 (1973). https://doi.org/10.1007/BF00519968

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