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Dopamine Synthesis by Non-Dopaminergic Neurons as an Effective Mechanism of Neuroplasticity

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Abstract

In addition to dopaminergic (DAergic) neurons, which possess all of the enzymes of dopamine synthesis (DA), there are neurons that express only one of the enzymes, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AAAD). These so-called monoenzymatic neurons are widely distributed in the brain and, in some areas, are even more numerous than dopaminergic (DAergic) neurons. Using in an vitro experimental approach that we developed it was first demonstrated that monoenzymatic neurons that contain complementary enzymes of DA synthesis, TH and AAAD, co-synthesize DA. L-3,4-dihydroxyphenylalanine (L-DOPA), which is synthesized from L-tyrosine in monoenzymatic TH-containing neurons, is transferred to monoenzymatic AAAD-containing neurons, where L-DOPA is converted to DA. We have also shown that cooperative synthesis of DA, although performed in some parts of the brain in the norm, is predominantly a manifestation of neuroplasticity in pathology. This additional source of DA synthesis contributes to compensation of the DA deficit, which occurs in neurodegenerative diseases such as hyperprolactinemia and Parkinson’s disease, whose pathogenesis is associated with degeneration of dopaminergic (DAergic) neurons. It is also possible that L-DOPA, which is secreted by monoenzymatic TH-containing neurons, plays the role of a neurotransmitter or neuromodulator and acts on target neurons through receptors to L-DOPA, DA, and norepinephrine. Thus, numerous non-dopaminergic monoenzymatic neurons, which are widely distributed in the brain, jointly synthesize DA, which is the most important mechanism of neuroplasticity; this compensates for the DA deficit during the degeneration of DAergic neurons.

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Abbreviations

VMAT2:

vesicular monoamine transporter 2

DA:

dopamine

DA-ergic:

dopaminergic

AAAD:

aromatic L-amino acid decarboxylase

L-DOPA:

L-3,4-dihydroxyphenylalanin

TH:

tyrosine hydroxylase

References

  1. Turpaev, T.M., Mediatornaya funktsiya atsetilkholina i priroda kholinoretseptora (Mediator Function of Acetylcholine and Nature of Cholinoreceptor), Moscow: AN SSSR, 1962.

    Google Scholar 

  2. Koshtojanz, Ch.S. and Turpaev, T.M., Nature, 1946, vol. 158, pp. 837–838.

    Article  Google Scholar 

  3. Björklund, A. and Lindvall, O., The Handbook of Chemical Neuroanatomy, Amsterdam: Elsevier, 1984, part 1, vol. 2, pp. 55–122.

    Google Scholar 

  4. Girault, J.A. and Greengard, P., Arch. Neurol., 2004, vol. 61, pp. 641–644.

    Article  PubMed  Google Scholar 

  5. Hökfelt, T., Johansson, O., and Goldstein, M., The handbook of chemical neuroanatomy, Amsterdam: Elsevier, 1984, part 1, vol. 2, pp. 157–276.

    Google Scholar 

  6. Hoffman, B.J., Hansson, S.R., Mezey, E., and Palkovits, M., Front. Neuroendocrinol., 1998, vol. 19, pp. 187–231.

    Article  CAS  PubMed  Google Scholar 

  7. Weihe, E. Depboylu, C., Schütz, B., Schäfer, M.K., and Eiden, L.E., Cell Mol. Neurobiol., 2006, vol. 26, pp. 659–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dahlstrom, A. and Fuxe, K., Acta Physiol. Scand., 1964, vol. 62, (Suppl. 232), pp. 1–55.

    Google Scholar 

  9. Palkovits, M. and Brownstein, M.J., Handbook of Chemical Neuroanatomy, Berlin: Springer, 1989, vol. 90/2, pp. 1–26.

    Google Scholar 

  10. Okamura, H., Kitahama, K., Nagatsu, I., and Geffard, M., Neurosci. Lett., 1988, vol. 95, pp. 347–353.

    Article  CAS  PubMed  Google Scholar 

  11. Meister, B.L., Hökfelt, T., Steinbusch, H.W., Skagerberg, G., Lindvall, O., Geffard, M., Joh, T.H., Cuello, A.C., and Goldstein, M., J. Chem. Neuroanat., 1988, vol. 1, pp. 59–64.

    CAS  PubMed  Google Scholar 

  12. Okamura, H., Kitahama, K., Raynaud, B., Nagatsu, I., Borri-Volttatorni, C., and Weber, M., Biomed. Res., 1988, vol. 9, pp. 261–267.

    Article  CAS  Google Scholar 

  13. Ugrumov, M.V., Adv. Pharmacol., 2013, vol. 68, pp. 37–91.

    Article  CAS  PubMed  Google Scholar 

  14. Zoli, M., Agnati, L.F., Tinner, B., Steinbusch, H., and Fuxe, K., J. Chem. Neuroanat., 1993, vol. 6, pp. 293–310.

    Article  CAS  PubMed  Google Scholar 

  15. Ershov, P.V., Ugrumov, M.V., Calas, A., Krieger, M., and Thibault, J., J. Comp. Neurol., 2002, vol. 446, pp. 114–122.

    Article  CAS  PubMed  Google Scholar 

  16. Kitahama, K., Ikemoto, K., Jouvet, A., Nagatsu, I., Sakamoto, N., and Pearson, J., J. Chem. Neuroanat., 1998, vol. 16, pp. 43–55.

    Article  CAS  PubMed  Google Scholar 

  17. Ershov, P.V., Ugrumov, M.V., Calas, A., Krieger, M., and Thibault, J., J. Chem. Neuroanat., 2005, vol. 30, pp. 27–33.

    Article  CAS  PubMed  Google Scholar 

  18. Ugrumov, M.V., Taxi, J., Pronina, T., Kurina, A., Sorokin, A., Sapronova, A., and Calas, A., Neuroscience, 2014, vol. 277, pp. 45–54.

    Article  CAS  PubMed  Google Scholar 

  19. Abramova, M., Marsais, F., Calas, A., Thibault, J., and Ugrumov, M., Brain Res., 2002, vol. 925, pp. 67–75.

    Article  CAS  PubMed  Google Scholar 

  20. Marsais, F., Parmentier, C., Terao, E., Taxi, J., and Calas, A., Microsc. Res. Tec., 2002, vol. 56, pp. 81–91.

    Article  CAS  Google Scholar 

  21. Ugrumov, M.V., J. Chem. Neuroanat., 2009, vol. 38, pp. 241–256.

    Article  CAS  PubMed  Google Scholar 

  22. Betarbet, R., Turner, R., Chockkan, V., DeLong, M.R., Allers, K.A., Walters, J., Levey, A.I., and Greenamyre, J.T., J. Comp. Neurol., 1997, vol. 17, pp. 6761–6768.

    CAS  Google Scholar 

  23. Tashiro, Y., Kaneko, T., Sugimoto, T., Nagatsu, I., Kikuchi, H., and Mizuno, N., Neurosci. Lett., 1989, vol. 100, pp. 29–34.

    Article  CAS  PubMed  Google Scholar 

  24. Tashiro, Y.L., Sugimoto, T., Hattori, T., Uemura, Y., Nagatsu, I., Kikuchi, H., and Mizuno, N., Neurosci. Lett., 1989, vol. 97, pp. 6–10.

    Article  CAS  PubMed  Google Scholar 

  25. Lopez-Real, A., Rodriguez-Pallares, J., Guerra, M.J., and Labandeira-Garcia, J.L., Brain Res., 2003, vol. 969, pp. 135–146.

    Article  CAS  PubMed  Google Scholar 

  26. Tandé, D., Höglinger, G., Debeir, T., Freundlieb, N., Hirsch, E.C., and Françis, C., Brain, 2006, vol. 129, pp. 1194–2000.

    Article  PubMed  Google Scholar 

  27. Cossette, M., Lecomte, F., and Parent, A., J. Chem. Neuroanat., 2005, vol. 29, pp. 1–11.

    Article  CAS  PubMed  Google Scholar 

  28. Dubach, M., Schmidt, R., Kunkel, D., Bowden, D.M., Martin, R., and German, D.C., Neurosci. Lett., 1987, vol. 75, pp. 205–210.

    Article  CAS  PubMed  Google Scholar 

  29. Cossette, M., Parent, A., and Lévesque, D., Eur. J. Comp. Neurol., 2004, vol. 20, pp. 2089–2095.

    Google Scholar 

  30. Huot, P., Lévesque, M., and Parent, A., Brain, 2007, vol. 130, pp. 222–232.

    Article  PubMed  Google Scholar 

  31. Ikemoto, K.L., Kitahama, K., Jouvet, A., Arai, R., Nishimura, A., Nishi, K., Nagatsu, I., Neurosci. Lett., 1997, vol. 232, pp. 111–114.

    Article  CAS  PubMed  Google Scholar 

  32. Okamura, H., Kitahama, K., Mons, N., Ibata, Y., Jouvet, M., and Geffard, M., Neurosci. Lett., 1988, vol. 95, pp. 42–46.

    Article  CAS  PubMed  Google Scholar 

  33. Mons, N., Tison, F., and Geffard, M., Synapse, 1989, vol. 4, pp. 99–105.

    Article  CAS  PubMed  Google Scholar 

  34. Melnikova, V.L., Orosco, N., Calas, A., Sapronova, A., Gainetdinov, R., Delhaye-Bouchaud, N., Nicolaidis, S., Rayevsky, K., and Ugrumov, M., Neuroscience, 1999, vol. 89, pp. 235–241.

    Article  CAS  PubMed  Google Scholar 

  35. Fisher, A., Biggs, C.S., Eradiri, O., and Starr, M.S., Neuroscience, 2000, vol. 95, pp. 97–111.

    Article  CAS  PubMed  Google Scholar 

  36. Misu, Y., Kitahama, K., and Goshima, Y., Pharmacol. Therapeut., 2003, vol. 97, pp. 117–137.

    Article  CAS  Google Scholar 

  37. Battaglia, A.A., Beltramo, M., Thibault, J., Krieger, M., and Calas, A., Brain Res., 1995, vol. 696, pp. 7–14.

    Article  CAS  PubMed  Google Scholar 

  38. Everitt, B., Meister, B., Hkfelt, T., Melander, T., Terenins, L., Rokaeus, A., Theodorsson-Norheim, E., Dockray, G., Edwardson, J., Cuello, C., Elde, R., Goldstein, M., Hemmings, H., Ouimet, C., Walaas, I., Greengard, P., Vale, W., Weber, E., Wu, J., and Chang, K., Brain Res., 1986, vol. 396, pp. 97–155.

    Article  CAS  PubMed  Google Scholar 

  39. Karasawa, N., Arai, R., Isomura, G., Nagatsu, T., and Nagatsu, I., Brain Res. Dev. Brain Res., 1997, vol. 99, pp. 121–125.

    Article  CAS  PubMed  Google Scholar 

  40. Okamura, H., Murakami, S., Chihara, K., Nagatsu, K., and Ibata, Y., Neuroendocrinology, 1985, vol. 41, pp. 177–179.

    Article  CAS  PubMed  Google Scholar 

  41. Tinner, B.L., Fuxe, K., Köhler, C., Hersh, l., Andersson, K., Jansson, A., Goldstein, M., and Agnati, l.F., Neurosci. Let., 1989, vol. 99, pp. 44–49.

    Article  CAS  Google Scholar 

  42. Verney, C., Gaspar, P., Febvret, A., and Berger, B., Brain Res., 1988, vol. 470, pp. 45–58.

    Article  CAS  PubMed  Google Scholar 

  43. Verney, C., el Amraoui, A., and Zecevic, N., Brain Res. Dev. Brain Res., 1996, vol. 97, pp. 251–259.

    Article  CAS  PubMed  Google Scholar 

  44. Izvolskaia, M., Duittoz, A.H., Ugrumov, M., and Tillet, Y., Brain Res., 2006, vol. 1083, pp. 29–38.

    Article  CAS  PubMed  Google Scholar 

  45. Ishida, Y.L., Yokoyama, C., Inatomi, T., Yagita, K., Dong, X., Yan, l., Yamaguchi, S., Nagatsu, I., Komori, T., Kitahama, K., and Okamura, H., Genes Cells, 2002, vol. 7, pp. 447–459.

    Article  CAS  PubMed  Google Scholar 

  46. Karasawa, N.L., Arai, R., Isomura, G., Yamada, K., Sakai, K., Sakai, M., Nagatsu, T., and Nagatsu, I., Neurosci. Lett., 1994, vol. 179, pp. 65–70.

    Article  CAS  PubMed  Google Scholar 

  47. Fernández, E., Torrents, D., Zorzano, A., Palacín, M., and Chillaron, J., J. Biol. Chem., 2005, vol. 280, pp. 19364–19372.

    Article  CAS  PubMed  Google Scholar 

  48. Jaeger, C.B., Ruggiero, D.A., Albert, V.R., Park, D.H., Joh, T.H., and Reis, D.J., The Handbook of Chemical Neuroanatomy, Amsterdam: Elsevier, 1984, vol. 2, pp. 387–408

    Google Scholar 

  49. Jaeger, C.B., Albert, V.R., Joh, T.H., and Reis, D.J., Brain Res., 1983, vol. 276, pp. 362–366.

    Article  CAS  PubMed  Google Scholar 

  50. Ugrumov, M.V., Handbook of Neurochemistry and Molecular Neurobiology, Boston: Springer, 2008, 3rd ed., pp. 21–73.

    Book  Google Scholar 

  51. Schneider, J.S., Rothblat, D.S., and DiStefano, L., Brain Res., 1994, vol. 643, pp. 86–91.

    Article  CAS  PubMed  Google Scholar 

  52. Balan, I.S., Ugrumov, M.V., Calas, A., Mailly, P., Krieger, M., and Thibault, J., J. Comp. Neurol., 2000, vol. 425, pp. 167–176.

    Article  CAS  PubMed  Google Scholar 

  53. Ugrumov, M.V., Melnikova, V.I., Lavrentyeva, A.V., Kudrin, V.S., and Rayevsky, K.S., Neuroscience, 2004, vol. 124, pp. 629–635.

    Article  CAS  PubMed  Google Scholar 

  54. Arai, R., Karasawa, N., Geffard, M., and Nagatsu, I., Neurosci. Lett., 1995, vol. 195, pp. 195–198.

    Article  CAS  PubMed  Google Scholar 

  55. Hayashi, M., Yamaji, Y., Kitajima, W., and Saruta, T., Am. J. Physiol., 1990, vol. 258, no. 1, part 2, pp. 28–33.

    Google Scholar 

  56. Meister, B., Fried, G., Holgert, H., Aperia, A., and Hokfelt, T., Kidney Int., vol. 42, pp. 617–623.

  57. Kozina, E.A., Kim, A.R., Kurina, A.Y., and Ugrumov, M.V., Neurobiol. D., vol. 98, no. is. 2017, pp. 108–121.

    Article  CAS  Google Scholar 

  58. Ugrumov, M.V., Khaindrava, V.G., Kozina, E.A., Kucheryanu, V.G., Bocharov, E.V., Kryzhanovsky, G.N., Kudrin, V.S., Narkevich, V.B., Klodt, P.M., Rayevsky, K.S., and Pronina, T.S., Neuroscience, 2011, vol. 181, pp. 175–188.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia

    M. V. Ugryumov

  2. ul. Vavilova 26, Moscow, 119334, Russia

    M. V. Ugryumov

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Correspondence to M. V. Ugryumov.

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Original Russian Text © M.V. Ugryumov, 2018, published in Neirokhimiya, 2018, Vol. 35, No. 4, pp. 281–288.

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Ugryumov, M.V. Dopamine Synthesis by Non-Dopaminergic Neurons as an Effective Mechanism of Neuroplasticity. Neurochem. J. 12, 288–294 (2018). https://doi.org/10.1134/S1819712418040086

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