Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal glands

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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Change history

  • 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

  1. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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

    Article  CAS  Google Scholar 

  3. 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

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. Barbeau A (1969) l-Dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. Can Med Assoc J 101:59–68

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 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

    Article  CAS  PubMed  Google Scholar 

  8. 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

    Article  CAS  Google Scholar 

  9. Bertler A, Rosengren E (1966) Possible role of brain dopamine. Pharmacol Rev 18:769–773

    CAS  PubMed  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. Birkmayer W, Hornykiewicz O (1961) The l-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia. Wien Klin Wochenschr 73:787–788

    CAS  Google Scholar 

  12. 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

    Article  CAS  Google Scholar 

  13. Blaschko H (1939) The specific action of l-dopa decarboxylase. J Physiol (Lond) 96:50–51

    CAS  Google Scholar 

  14. 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

    CAS  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Carlsson A (1959) The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev 11:490–493

    CAS  PubMed  Google Scholar 

  17. Carlsson A (1971) Basic concepts underlying recent developments in the field of Parkinson’s disease. Contemp Neurol Ser 8:1–31

    CAS  PubMed  Google Scholar 

  18. Carlsson A (1993) On the neuronal circuitries and neurotransmitters involved in the control of locomotor activity. J Neural Transm Suppl 40:1–12

    Article  CAS  PubMed  Google Scholar 

  19. Carlsson A (2001) A paradigm shift in brain research. Science 294:1021–1024. https://doi.org/10.1126/science.1066969

    Article  CAS  PubMed  Google Scholar 

  20. 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

    Article  CAS  PubMed  Google Scholar 

  21. 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

    CAS  PubMed  Google Scholar 

  22. Carlsson A, Lindqvist M, Magnusson T, Waldeck B (1958) On the presence of 3-hydroxytyramine in brain. Science 127:471

    Article  CAS  PubMed  Google Scholar 

  23. 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

    CAS  PubMed  Google Scholar 

  24. Carlsson A, Falck B, Hillarp NA (1962) Cellular localization of brain monoamines. Acta Physiol Scand Suppl 56:1–28

    Article  CAS  PubMed  Google Scholar 

  25. 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

    Article  CAS  PubMed  Google Scholar 

  26. Dahlström A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20:398–399

    Article  PubMed  Google Scholar 

  27. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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

    Article  CAS  PubMed  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

  30. 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

    Article  PubMed  PubMed Central  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    CAS  PubMed  Google Scholar 

  33. 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

    Article  CAS  PubMed  Google Scholar 

  34. Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. 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

    Article  PubMed  Google Scholar 

  37. 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

    CAS  PubMed  Google Scholar 

  38. 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

    PubMed  Google Scholar 

  39. 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

    PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  41. 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

    Google Scholar 

  42. 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

    Article  CAS  PubMed  Google Scholar 

  43. 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

    Article  CAS  PubMed  Google Scholar 

  44. 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

    Article  CAS  PubMed  Google Scholar 

  45. 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

    Article  CAS  PubMed  Google Scholar 

  46. 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

    Article  CAS  PubMed  Google Scholar 

  47. 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

    CAS  PubMed  Google Scholar 

  48. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J Biol Chem 239:2910–2917

    CAS  PubMed  Google Scholar 

  50. 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

    CAS  PubMed  Google Scholar 

  51. 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

    Article  CAS  PubMed  Google Scholar 

  52. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 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

    Article  CAS  Google Scholar 

  54. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Richardson DS, Lichtman JW (2015) Clarifying tissue clearing. Cell 162:246–257. https://doi.org/10.1016/j.cell.2015.06.067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 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

    Article  CAS  PubMed  Google Scholar 

  57. 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

    Article  CAS  PubMed  Google Scholar 

  58. 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

    Article  CAS  PubMed  Google Scholar 

  59. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sladek JR, Björklund A (1982) Preface. Brain Res Bull 9:9–10

    Google Scholar 

  61. 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

    Article  PubMed  PubMed Central  Google Scholar 

  62. 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

    Article  CAS  PubMed  Google Scholar 

  63. 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

    Article  CAS  PubMed  Google Scholar 

  64. 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

    Article  CAS  PubMed  Google Scholar 

  65. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 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

    Article  CAS  PubMed  Google Scholar 

  68. 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

    Article  PubMed  Google Scholar 

  69. 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

    Article  PubMed  Google Scholar 

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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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Correspondence to William Rostène.

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Movie 1

Supplementary material 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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Keywords

  • Tyrosine hydroxylase
  • Dopamine mapping
  • Mouse brain
  • Adrenals
  • Clearing
  • iDISCO+