Abstract
Working on catecholamine systems for years, the neuropharmacologist Arvid Carlsson has made a number of important and pioneering discoveries, which have highlighted the key role of these neuronal and peripheral neurotransmitters in brain functions and adrenal regulations. Since then, major advances have been made concerning the distribution of the catecholaminergic systems in particular by studying their rate-limiting enzyme, tyrosine hydroxylase (TH). Recently new methods of tissue transparency coupled with in toto immununostaining and three-dimensional (3D) imaging technologies allow to precisely map TH immunoreactive pathways in the mouse brain and adrenal glands. High magnification images and movies obtained with combined technologies (iDISCO+ and light-sheet microscopy) are presented in this review dedicated to the pioneer work of Arvid Carlsson and his collaborators.
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17 November 2018
Unfortunately, the given name and family name of the fourth author was incorrectly tagged in the xml data, therefore it is abbreviated wrongly as ‘‘Goazigo AR’’ in Pubmed. The correct given name is Annabelle and family name is Reaux‑Le Goazigo.
References
Ait-Ali D, Turquier V, Tanguy Y, Thouennon E, Ghzili H, Mounien L, Derambure C, Jegou S, Salier JP, Vaudry H, Eiden LE, Anouar Y (2008) Tumor necrosis factor (TNF)-alpha persistently activates nuclear factor-kappaB signaling through the type 2 TNF receptor in chromaffin cells: implications for long-term regulation of neuropeptide gene expression in inflammation. Endocrinology 149:2840–2852. https://doi.org/10.1210/en.2007-1192
Anden NE, Carlsson A, Dahlström A, Fuxe K, Hillarp NA, Larsson K (1964) Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci 3:523–530
Anden NE, Dahlström A, Fuxe K, Larsson K (1965) Mapping out of catecholamine and 5-hydroxytryptamine neurons innervating the telencephalon and diencephalon. Life Sci 4:1275–1279
Azaripour A, Lagerweij T, Scharfbillig C, Jadczak AE, Willershausen B, Van Noorden CJ (2016) A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue. Prog Histochem Cytochem 51:9–23. https://doi.org/10.1016/j.proghi.2016.04.001
Balan IS, Ugrumov MV, Calas A, Mailly P, Krieger M, Thibault J (2000) Tyrosine hydroxylase-expressing and/or aromatic l-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of perinatal rats: differentiation and sexual dimorphism. J Comp Neurol 425:167–176
Barbeau A (1969) l-Dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. Can Med Assoc J 101:59–68
Belle M, Godefroy D, Dominici C, Heitz-Marchaland C, Zelina P, Hellal F, Bradke F, Chedotal A (2014) A simple method for 3D analysis of immunolabeled axonal tracts in a transparent nervous system. Cell Rep 9:1191–1201. https://doi.org/10.1016/j.celrep.2014.10.037
Belle M, Godefroy D, Couly G, Malone SA, Collier F, Giacobini P, Chedotal A (2017) Tridimensional visualization and analysis of early human development. Cell 169:161–173. https://doi.org/10.1016/j.cell.2017.03.008
Bertler A, Rosengren E (1966) Possible role of brain dopamine. Pharmacol Rev 18:769–773
Bertler A, Falck B, Gottfries CG, Ljunggren L, Rosengren E (1964) Soeme observations on adrenergic connections between mesencephalon and cerebral hemispheres. Acta Pharmacol Toxicol (Copenh) 21:283–289
Birkmayer W, Hornykiewicz O (1961) The l-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia. Wien Klin Wochenschr 73:787–788
Björklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30:194–202. https://doi.org/10.1016/j.tins.2007.03.006
Blaschko H (1939) The specific action of l-dopa decarboxylase. J Physiol (Lond) 96:50–51
Bornstein SR, Gonzalez-Hernandez JA, Ehrhart-Bornstein M, Alder G, Scherbaum WA (1994) Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions. J Clin Endocrinol Metab 78(1):225–232
Bunn SJ, Ait-Ali D, Eiden LE (2012) Immune-neuroendocrine integration at the adrenal gland: cytokine control of the adrenomedullary transcriptome. J Mol Neurosci 48:413–419. https://doi.org/10.1007/s12031-012-9745-1
Carlsson A (1959) The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev 11:490–493
Carlsson A (1971) Basic concepts underlying recent developments in the field of Parkinson’s disease. Contemp Neurol Ser 8:1–31
Carlsson A (1993) On the neuronal circuitries and neurotransmitters involved in the control of locomotor activity. J Neural Transm Suppl 40:1–12
Carlsson A (2001) A paradigm shift in brain research. Science 294:1021–1024. https://doi.org/10.1126/science.1066969
Carlsson A, Hillarp NA (1956) Release of adenosine triphosphate along with adrenaline and noradrenaline following stimulation of the adrenal medulla. Acta Physiol Scand 37:235–239. https://doi.org/10.1111/j.1748-1716.1956.tb01359.x
Carlsson A, Hillarp NA, Hökfelt B (1957) The concomitant release of adenosine triphosphate and catechol amines from the adrenal medulla. J Biol Chem 227:243–252
Carlsson A, Lindqvist M, Magnusson T, Waldeck B (1958) On the presence of 3-hydroxytyramine in brain. Science 127:471
Carlsson A, Falck B, Hillarp NA, Thieme G, Torp A (1961) A new histochemical method for visualization of tissue catechol amines. Med Exp Int J Exp Med 4:123–125
Carlsson A, Falck B, Hillarp NA (1962) Cellular localization of brain monoamines. Acta Physiol Scand Suppl 56:1–28
Cavadas C, Grand D, Mosimann F, Cotrim MD, Ribeiro F, Brunner CA, Grouzmann HR, E (2003) Angiotensin II mediates catecholamine and neuropeptide Y secretion in human adrenal chromaffin cells through the AT1 receptor. Regul Pept 111:61–65
Dahlström A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20:398–399
Dobosz M, Ntziachristos V, Scheuer W, Strobel S (2014) Multispectral fluorescence ultramicroscopy: three-dimensional visualization and automatic quantification of tumor morphology, drug penetration, and antiangiogenic treatment response. Neoplasia 16:1–13
Dodt HU, Leischner U, Schierloh A, Jahrling N, Mauch CP, Deininger K, Deussing JM, Eder M, Zieglgansberger W, Becker K (2007) Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat Methods 4:331–336. https://doi.org/10.1038/nmeth1036
Ehrhart-Bornstein M, Bornstein SR (2008) Cross-talk between adrenal medulla and adrenal cortex in stress. Ann N Y Acad Sci 1148:112–117. https://doi.org/10.1196/annals.1410.053
Epp JR, Niibori Y, Hsiang L, Mercaldo HL, Deisseroth V, Josselyn K, Frankland SA, P.W (2015) Optimization of CLARITY for clearing whole-brain and other intact organs. eNeuro. https://doi.org/10.1523/ENEURO.0022-15.2015
Erturk A, Becker K, Jahrling N, Mauch CP, Hojer CD, Egen JG, Hellal F, Bradke F, Sheng M, Dodt HU (2012) Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc 7:1983–1995. https://doi.org/10.1038/nprot.2012.119
Falck B, Torp A (1962) New evidence for the localization of noradrenalin in the adrenergic nerve terminals. Med Exp Int J Exp Med 6:169–172
Falck B, Hillarp NA, Thieme G, Torp A (1982) Fluorescence of catechol amines and related compounds condensed with formaldehyde. Brain Res Bull 9:xi–xv
Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, New York
Gallo-Payet N, Pothier P, Isler H (1987) On the presence of chromaffin cells in the adrenal cortex: their possible role in adrenocortical function. Biochem Cell Biol 65(6):588–592
Godefroy D, Dominici C, Hardin-Pouzet H, Anouar Y, Melik-Parsadaniantz S, Rostene W, Reaux-Le Goazigo A (2017) Three-dimensional distribution of tyrosine hydroxylase, vasopressin and oxytocin neurones in the transparent postnatal mouse brain. J Neuroendocrinol. https://doi.org/10.1111/jne.12551
Hillarp NA, Nilson B (1954) The structure of the adrenaline and noradrenaline containing granules in the adrenal medullary cells with reference to the storage and release of the sympathomimetic amines. Acta Physiol Scand Suppl 31:79–107
Hökfelt T, Johansson O, Fuxe K, Goldstein M, Park D (1976) Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon. Med Biol 54:427–453
Hökfelt T, Johansson O, Fuxe K, Goldstein M, Park D (1977) Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain II. Tyrosine hydroxylase in the telencephalon. Med Biol 55:21–40
Hökfelt T, Everitt B, Meister B, Melander T, Schalling M, Johansson O, Lundberg JM, Hulting AL, Werner S, Cuello C et al (1986) Neurons with multiple messengers with special reference in neuroendocrine systems. Recent Prog Horm Res 42:1–70
Hökfelt T, Martensson R, Björklund A, Kleinau S, Goldstein M (1984) Distributional maps of tyrosine-hydroxylase-immunoreactive neurons in the rat brain. In: Hökfelt T (ed) Handbook of chemical neuroanatomy. Classical transmitters in the CNS, part I. Elsevier, Amsterdam, pp 277–379
Klingberg A, Hasenberg A, Ludwig-Portugall I, Medyukhina A, Mann L, Brenzel A, Engel DR, Figge MT, Kurts C, Gunzer M (2017) Fully automated evaluation of total glomerular number and capillary tuft size in nephritic kidneys using lightsheet microscopy. J Am Soc Nephrol 28:452–459. https://doi.org/10.1681/ASN.2016020232
Kramer EE, Steadman PE, Epp JR, Frankland PW, Josselyn SA (2018) Assessing individual neuronal activity across the intact brain: using hybridization chain reaction (HCR) to detect arc mRNA localized to the nucleus in volumes of cleared brain tissue. Curr Protoc Neurosci 84:e49. https://doi.org/10.1002/cpns.49
Kvetnansky R, Weise VK, Kopin IJ (1970) Elevation of adrenal tyrosine hydroxylase and phenylethanolamine-N-methyl transferase by repeated immobilization of rats. Endocrinology 87:744–749. https://doi.org/10.1210/endo-87-4-744
Launay PS, Godefroy D, Khabou H, Rostene W, Sahel JA, Baudouin C, Parsadaniantz M, Goazigo SReaux-Le, A (2015) Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion. Exp Eye Res 139:136–143. https://doi.org/10.1016/j.exer.2015.06.008
Lindvall O, Björklund A, Skagerberg G (1984) Selective histochemical demonstration of dopamine terminal systems in rat di- and telencephalon: new evidence for dopaminergic innervation of hypothalamic neurosecretory nuclei. Brain Res 306:19–30
Markey KA, Kondo H, Shenkman L, Goldstein M (1980) Purification and characterization of tyrosine hydroxylase from a clonal pheochromocytoma cell line. Mol Pharmacol 17:79–85
Moore AM, Lucas KA, Goodman RL, Coolen LM, Lehman MN (2018) Three-dimensional imaging of KNDy neurons in the mammalian brain using optical tissue clearing and multiple-label immunocytochemistry. Sci Rep 8:2242. https://doi.org/10.1038/s41598-018-20563-2
Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J Biol Chem 239:2910–2917
Nobin A, Björklund A (1973) Topography of the monoamine neuron systems in the human brain as revealed in fetuses. Acta Physiol Scand Suppl 388:1–40
Pan C, Cai R, Quacquarelli FP, Ghasemigharagoz A, Lourbopoulos A, Matryba P, Plesnila N, Dichgans M, Hellal F, Erturk A (2016) Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Nat Methods 13:859–867. https://doi.org/10.1038/nmeth.3964
Qi Y, Zhang XJ, Renier N, Wu Z, Atkin T, Sun Z, Ozair MZ, Tchieu J, Zimmer B, Fattahi F, Ganat Y, Azevedo R, Zeltner N, Brivanlou AH, Karayiorgou M, Gogos J, Tomishima M, Tessier-Lavigne M, Shi SH, Studer L (2017) Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat Biotechnol 35:154–163. https://doi.org/10.1038/nbt.3777
Renier N, Wu Z, Simon DJ, Yang J, Ariel P, Tessier-Lavigne M (2014) iDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging. Cell 159:896–910. https://doi.org/10.1016/j.cell.2014.10.010
Renier N, Adams EL, Kirst C, Wu Z, Azevedo R, Kohl J, Autry AE, Kadiri L, Umadevi Venkataraju K, Zhou Y, Wang VX, Tang CY, Olsen O, Dulac C, Osten P, Tessier-Lavigne M (2016) Mapping of brain activity by automated volume analysis of immediate early genes. Cell 165:1789–1802. https://doi.org/10.1016/j.cell.2016.05.007
Richardson DS, Lichtman JW (2015) Clarifying tissue clearing. Cell 162:246–257. https://doi.org/10.1016/j.cell.2015.06.067
Rosmaninho-Salgado J, Araujo IM, Alvaro AR, Mendes AF, Ferreira L, Grouzmann E, Mota A, Duarte EP, Cavadas C (2009) Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1beta: role of neuropeptide Y and nitric oxide. J Neurochem 109:911–922. https://doi.org/10.1111/j.1471-4159.2009.06023.x
Senthilkumaran M, Johnson ME, Bobrovskaya L (2016) The effects of insulin-induced hypoglycaemia on tyrosine hydroxylase phosphorylation in rat brain and adrenal gland. Neurochem Res 41:1612–1624. https://doi.org/10.1007/s11064-016-1875-3
Seroogy K, Tsuruo Y, Hökfelt T, Walsh J, Fahrenkrug J, Emson PC, Goldstein M (1988) Further analysis of presence of peptides in dopamine neurons. Cholecystokinin, peptide histidine-isoleucine/vasoactive intestinal polypeptide and substance P in rat supramammillary region and mesencephalon. Exp Brain Res 72:523–534
Simmons DM, Swanson LW (2008) High-resolution paraventricular nucleus serial section model constructed within a traditional rat brain atlas. Neurosci Lett 438:85–89. https://doi.org/10.1016/j.neulet.2008.04.057
Sladek JR, Björklund A (1982) Preface. Brain Res Bull 9:9–10
Soderblom C, Lee DH, Dawood A, Carballosa M, Jimena Santamaria A, Benavides FD, Jergova S, Grumbles RM, Thomas CK, Park KK, Guest JD, Lemmon VP, Lee JK, Tsoulfas P (2015) 3D imaging of axons in transparent spinal cords from rodents and nonhuman primates. eNeuro. https://doi.org/10.1523/ENEURO.0001-15.2015
Sotelo C, Javoy F, Agid Y, Glowinski J (1973) Injection of 6-hydroxydopamine in the substantia nigra of the rat. I. Morphological study. Brain Res 58:269–290
Tamminga CA, Carlsson A (2002) Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr Drug Targets CNS Neurol Disord 1:141–147
Ugrumov M, Melnikova V, Ershov P, Balan I, Calas A (2002) Tyrosine hydroxylase- and/or aromatic l-amino acid decarboxylase-expressing neurons in the rat arcuate nucleus: ontogenesis and functional significance. Psychoneuroendocrinology 27:533–548
Vigouroux RJ, Belle M, Chedotal A (2017) Neuroscience in the third dimension: shedding new light on the brain with tissue clearing. Mol Brain 10:33. https://doi.org/10.1186/s13041-017-0314-y
Vogt M (1954) The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J Physiol 123:451–481
Waymire JC, Weiner N, Schneider FH, Goldstein M, Freedman LS (1972) Tyrosine hydroxylase in human adrenal and pheochromocytoma: localization, kinetics, and catecholamine inhibition. J Clin Investig 51:1798–1804. https://doi.org/10.1172/JCI106981
Yeo SH, Kyle V, Morris PG, Jackman S, Sinnett-Smith LC, Schacker M, Chen C, Colledge WH (2016) Visualisation of Kiss1 neurone distribution using a Kiss1-CRE transgenic mouse. J Neuroendocrinol. 28. https://doi.org/10.1111/jne.12435
Zhu X, Xia Y, Wang X, Si K, Gong W (2017) Optical brain imaging: a powerful tool for neuroscience. Neurosci Bull 33:95–102. https://doi.org/10.1007/s12264-016-0053-6
Acknowledgements
The present study was supported by Sorbonne and Normandie Universities, the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Association Française d’Epargne et de Retraite (AFER). Images were obtained on PRIMACEN (http://www.primacen.fr), the Cell Imaging Platform of Normandy, IRIB, Faculty of Sciences, University of Rouen, 76821 Mont-Saint-Aignan.
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Supplementary material 1 Movie 1 3D movie of TH distribution in P5 mouse brain. Attribution of false colors and volume “rendering” for dopaminergic (blue, in the striatum and mesencephalic regions), various catecholamines (green, in the hypothalamus), noradrenergic (white, in the olfactory bulbs and yellow, in the pons), noradrenergic/adrenergic neurons (pink, in the brainstem). The cerebellum is in orange (AVI 96719 KB)
Supplementary material 2 Movie 2 3D movie of the localization of TH positive chromaffin cells in the adrenal medulla of adult mice (MP4 28586 KB)
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Godefroy, D., Rostène, W., Anouar, Y. et al. Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal glands. J Neural Transm 126, 367–375 (2019). https://doi.org/10.1007/s00702-018-1925-x
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DOI: https://doi.org/10.1007/s00702-018-1925-x