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Cholinergic systems of the rat brain and neuronal reorganization under conditions of acute hypoxia

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Abstract

We studied the role of cholinergic systems of the rat brain in the mechanisms of acute response of the neocortex and hippocampus to acute hypobaric hypoxia. The activity of choline acetyltransferase and Na/K-ATPase and the protein content were measured in subfractions of synaptic membranes and the synaptoplasm of “light” and “heavy” synaptosomes. The same biochemical indices were measured in fractions of light and heavy synaptosomes from the nucleus of the solitary tract of the medulla oblongata. In the neocortex, we analyzed the ultrastructure of the synaptic pool. We found active involvement of cholinergic systems in the response to acute hypoxia in all brain structures studied. The synapses of cholinergic projection neurons from the basal nuclei of the frontal cortex (light fractions of synaptosomes), neocortical interneurons (heavy fractions of synaptosomes), and, presumably, GABAergic interneurons of the hippocampus (heavy fraction) were the most sensitive to hypoxia. At the limit of resistance to hypoxia, increased metabolic activity predominated in the synapses of rats that had poorly resistance to hypoxia, while in highly resistant rats this activity was diminished. This difference is related to the different duration of their exposure to critical altitude. We found a reduction in the number of synapses and staging in the development of the functional response of synapses to acute hypoxia. We propose a mechanism for the structural and functional reorganization of synaptic links during acute hypoxia, which is general for both poorly and highly resistant rats. We also hypothesize that a reduction of synapses is one of early triggers that switches neurons to levels of interaction that are adequate for hypoxia.

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References

  1. von Engelhardt, J., Eliava, M., Meyer, A.H., Rozov, A., and Monyer, H., J. Neurosci., 2007, vol. 27, no. 21, pp. 5633–5642.

    Article  Google Scholar 

  2. Khazipov, R., Congar, P., and Ben-Ari, Y., J. Neurophysiol., 1995, vol. 74, no. 5, pp. 2138–2149.

    CAS  PubMed  Google Scholar 

  3. Sadoshima, S., Ibayashi, S., Fujii, K., Nagao, T., Sugimori, H., and Fujishima, M., J. Cereb. Blood Flow Metab., 1995, vol. 15, no. 3, pp. 845–851.

    CAS  PubMed  Google Scholar 

  4. Riepe, M.W., Eur. J. Neurol., 2005, Suppl. 3, pp. 3–9.

  5. Fujiki, M., Kobayashi, H., Uchida, S., Inoue, R., and Ishii, K., Brain Res., 2005, vol. 1043, nos. 1–2, pp. 36–41.

    Google Scholar 

  6. Rossner, S., Schliebs, R., and Bigl, V., Brain Res., 1995, vol. 696, nos. 1–2, pp. 165–176.

    CAS  PubMed  Google Scholar 

  7. Clough, R.W., Neese, S.L., Sherill, L.K., Tan, A.A., Duke, A., Roosevelt, R.W., Browning, R.A., and Smith, D.C., Neuroscience, 2007, vol. 147, no. 2, pp. 286–293.

    Article  CAS  PubMed  Google Scholar 

  8. Neese, S.L., Sherill, L.K., Tan, A.A., Roosevelt, R.W., Browning, R.A., Smith, D.C., Duke, A., and Clough, R.W., Brain Res., 2007, vol. 1128, no. 1, pp. 157–163.

    Article  CAS  PubMed  Google Scholar 

  9. Iwasaki, K., Kitamura, Y., Ohgami, Y., Mishima, K., and Fujiwara, M., Brain Res., 1996, vol. 709, no. 2, pp. 163–172.

    Article  CAS  PubMed  Google Scholar 

  10. Lipton, P., Physiol. Rev., 1999, vol. 79, no. 4, pp. 1431–1568.

    CAS  PubMed  Google Scholar 

  11. Ogawa, N., Haba, K., Asanuma, M., Mizukawa, K., and Mori, A., in Neuroreceptor Mechanisms in Brain, Kito, S., et al., Eds., New York: Plenum., 1991, pp. 343–347.

    Google Scholar 

  12. Ishimaru, H., Takahashi, A., Ikarashi, Y., and Maruyama, Y., Brain Res., 1998, vol. 789, no. 2, pp. 194–200.

    Article  CAS  PubMed  Google Scholar 

  13. O’Neill, M., Canney, M., Earley, B., Junien, J.L., and Leonard, B.E., Neurochem. Int., 1996, vol. 28, no. 2, pp. 193–207.

    Article  PubMed  Google Scholar 

  14. Tanaka, K., Wada, N., Hori, K., Asanuma, M., Nomura, M., and Ogawa, N., J. Neurosci. Methods, 1998, vol. 84, nos. 1–2, pp. 63–68.

    Article  CAS  PubMed  Google Scholar 

  15. Ni, J.W., Matsumoto, K., and Watanabe, H., Jpn. J. Pharmacol., 1995, vol. 67, no. 2, pp. 37–41.

    Article  Google Scholar 

  16. Watanabe, H., Ni, J.W., Sakai, Y., Matsumoto, K., Murakami, Y., and Tohda, M., Nihon Shinkei Seishin Yakurigaku Zasshi, 1996, vol. 16, no. 1, pp. 19–24.

    CAS  PubMed  Google Scholar 

  17. Onodera, H., Sato, G., and Kogure, K., Brain Res., 1987, vol. 415, no. 2, pp. 309–322.

    Article  CAS  PubMed  Google Scholar 

  18. Zakharova, E.I., Svinov, M.M., Germanova, E.L., Fedorova, M.M., and Luk’yanova, L.D., Problemy gipoksii: molekulyarnye, fiziologicheskie i meditsinskie aspekty (Problems of Hypoxia: Molecular, Physiological, and Medical Aspects) Luk’yanova, L.D., Ushakov, I.B, Eds., Voronezh: Istoki, 2004, pp. 268–296.

    Google Scholar 

  19. Zakharova, E.I, Storojeva, Z.I, Germanova, E.L, Monakov, M.Y, Proshin, A.T, Dudchenko, A.M, and Lukyanova, L.D, in Adaptation Biol. Med. (V. 5: Health Potentials), Lukyanova, L., Takeda, N., and Singal, P.K., Eds., New Delhi, India: Narosa Publishing House Pvt. Ltd, 2008, pp. 122–141.

    Google Scholar 

  20. Uematsu, D., Greenberg, J.H., Reivich, M., and Karp, A., Ann. Neurol., 1988, vol. 24, no. 3, pp. 420–428.

    Article  CAS  PubMed  Google Scholar 

  21. Semchenko, V.V., Bogolepov, N.N., and Stepanov, S.S., Sinaptoarkhitektonika kory bol’shogo mozga (Synaptic Architecture of the Brain Cortex), Omsk: Omskaya oblastnaya tipografiya, 1995.

    Google Scholar 

  22. Sims, N.R., Metab. Brain Dis, 1995, vol. 10, no. 3, pp. 191–217.

    Article  CAS  PubMed  Google Scholar 

  23. Chernobaeva, G.N. and Luk’yanova, L.D., Farmakologicheskaya korrektsiya gipoksicheskikh sostoyanii (Pharmacological Correction of Hypoxic States), Moscow, 1989, pp. 160–164.

  24. Zakharova, E.I., Dudchenko, A.M., Svinov, M.M., Ivanov, D.S., and Ignat’ev, I.V., Neirokhimiya, 2001, vol. 18, no. 2, pp. 119–131.

    CAS  Google Scholar 

  25. Tsainer, B., Orlova, E.I., and Belichenko, P.V., Zh. Nevropatol. i Psikhiatr., 1991, vol. 91, no. 12, pp. 39–43.

    CAS  Google Scholar 

  26. Fonnum, F., Biochem. J., 1969, vol. 115, pp. 465–472.

    CAS  PubMed  Google Scholar 

  27. Pullman, M.E., Penevsky, H.S., Datta, A., and Racker, E.J., Biol. Chem., 1960, vol. 235, no. 11, pp. 3322–3329.

    CAS  Google Scholar 

  28. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R., J. Biol. Chem., 1959, vol. 193, pp. 265–275.

    Google Scholar 

  29. Kobzar’, A.I., Prikladnaya matematicheskaya statistika. Dlya inzhenerov i nauchnykh rabotnikov (Applied Mathematical Statistics. For Engineers and Scientists), Moscow: Fizmatlit, 2006.

    Google Scholar 

  30. Mukhin, E.L., Zakharova, E.I., and Kikteva, E.A., Neurosci. Behav. Physiol., 2002, vol. 32, no. 4, pp. 379–387.

    Article  CAS  PubMed  Google Scholar 

  31. Cooke, L.J. and Rylett, R.J., Brain Res., 1997, vol. 751, no. 2, pp. 232–238.

    Article  CAS  PubMed  Google Scholar 

  32. Dobransky, T., Davis, W.L., Xiao, G.H., and Rylett, R.J., Biochem. J., 2000, vol. 349, pp. 141–151.

    Article  CAS  PubMed  Google Scholar 

  33. Dobransky, T., Davis, W.L., and Rylett, R.J., J. Biol. Chem., 2001, vol. 276, issue 25, pp. 22224–22250.

    Article  Google Scholar 

  34. Sha, D., Jin, H., Kopke, R.D., and Wu, J.Y., Neurochem. Res, 2004, vol. 29, no. 1, pp. 199–207.

    Article  CAS  PubMed  Google Scholar 

  35. Rylett, R.J., J. Neurochem., 1989, vol. 52, no. 3, pp. 869–875.

    Article  CAS  PubMed  Google Scholar 

  36. Schmidt, B.M. and Rylett, R.J., J. Neurochem., 1993a, vol. 61, no. 5, pp. 1774–1781.

    Article  CAS  PubMed  Google Scholar 

  37. Schmidt, B.M. and Rylett, R.J., Neuroscience, 1993b, vol. 54, no. 3, pp. 649–656.

    Article  CAS  PubMed  Google Scholar 

  38. Maevskii, E.I., Rozenfel’d, A.S., Grishina, E.V., and Kondrashova, M.N., Korrektsiya metabolicheskogo atsidoza putem podderzhaniya funktsii mitokhondrii (Correction of Metabolic Acidosis by Support of Mitochondrial Function), Pushchino, 2001.

  39. Belousova, V.V., Dudchenko, A.M., and Luk’yanova, L.D., Byul. Eksper. Biol. and Medic., 1992, vol. 114, no. 12, pp. 588–590.

    CAS  Google Scholar 

  40. Anderson, K.J., Gibbs, R.B., Salvaterra, P.M., and Cotman, C.W., J. Comp. Neurol., 1986, vol. 249, no. 2, pp. 279–292.

    Article  CAS  PubMed  Google Scholar 

  41. Matthews, D.A., Salvaterra, P.M., Crawford, G.D., Houser, C.R., and Vaughn, J.E., Brain Res., 1987, vol. 402, no. 1, pp. 30–43.

    Article  CAS  PubMed  Google Scholar 

  42. Frotscher, M., Vida, I., and Bender, R., Neuroscience, 2000, vol. 96, no. 1, pp. 27–31.

    Article  CAS  PubMed  Google Scholar 

  43. Saper, C.B., J. Comp. Neurol., 1984, vol. 222, no. 3, pp. 313–342.

    Article  CAS  PubMed  Google Scholar 

  44. Malyshev, A.Yu., Luk’yanova, L.D., and Krapivin, S.V., Byul. Eksper. Biol. and Medic., 1996, vol. 122, no. 9, pp. 264–267.

    Google Scholar 

  45. Ferguson, D.G., Haxhiu, M.A., To, A.J., Erokwu, B., and Dreshaj, I.A., Neurosci. Lett., 2000, vol. 287, no. 2, pp. 141–145.

    Article  CAS  PubMed  Google Scholar 

  46. Tarakanov, I.A. and Safanov, V.A., Patogenez, 2003, no. 2, pp. 11–24.

  47. Haxhiu, M.A., Kc, P., Moore, C.T., Acquah, S.S., Wilson, C.G., Zaidi, S.I., Massari, V.J., and Ferguson, D.G., J. Appl. Physiol., 2005, vol. 98, no. 6, pp. 1961–1982.

    Article  CAS  PubMed  Google Scholar 

  48. Schäfer, M.K., Eiden, L.E., and Weihe, E., Neuro-science, 1998, vol. 84, no. 2, pp. 331–359.

    Google Scholar 

  49. Tsyrlin, V.A. and Khrustaleva, R.S., Vestnik Aritmologii, 2001, no. 22, pp. 75–80.

  50. Khitrov, N.K., Byul. Eksper. Biol. i Medic., 1998, vol. 125, no. 6, pp. 604–611.

    Article  CAS  Google Scholar 

  51. Huang, Z.G., Griffioen, K.J., Wang, X., Dergacheva, O., Kamendi, H., Gorini, C., and Mendelowitz, D., J. Neurophysiol., 2007, vol. 98, no. 4, pp. 2429–2438.

    Article  CAS  PubMed  Google Scholar 

  52. He, L., Dinger, B., and Fidone, S., J. Appl. Physiol., 2005, vol. 8, no. 2, pp. 614–619.

    Google Scholar 

  53. Butler, J.A., Anand, A., Crawford, M.R., Glanfille, A.R., McKensie, D.K., Paintal, A.S., Talor, J.L., and Gandevia, S.C., J. Physiol., 2001, vol. 534, no. 2, pp. 283–293.

    Article  Google Scholar 

  54. Greenberg, J.H., Uematsu, D., Araki, N., and Reivich, M., Arzneimittelforschung, 1991, vol. 41, no. 3A, pp. 324–333.

    CAS  PubMed  Google Scholar 

  55. Celsi, F., Pizzo, P., Brini, M., Leo, S., Fotino, C., Pinton, P., and Rizzuto, R., Biochim. Biophys. Acta, 2009, vol. 1787, no. 5, pp. 335–344.

    Article  CAS  PubMed  Google Scholar 

  56. Dobransky, T. and Rylett, R.J., J. Neurochem., 2005, vol. 95, no. 2, pp. 305–313.

    Article  CAS  PubMed  Google Scholar 

  57. Medvedeva, Y.V., Lin, B., Shuttleworth, C.W., and Weiss, J.H., J. Neurosci., 2009, vol. 29, no. 4, pp. 1105–1114.

    Article  CAS  PubMed  Google Scholar 

  58. Bahar, S., Fayuk, D., Somjen, G.G., Aitken, P.G., and Turner, D.A., J. Neurophysiol., 2000, vol. 84, no. 1, pp. 311–324.

    CAS  PubMed  Google Scholar 

  59. Smith, L.K. and Carroll, P.T., Brain Res., 1993, vol. 605, no. 1, pp. 155–163.

    Article  CAS  PubMed  Google Scholar 

  60. Glebov, R.N. and Kryzhanovskii, G.N., Usp. Fiziol. Nauk, 1975, vol. 6, no. 4, pp. 3–33.

    CAS  PubMed  Google Scholar 

  61. Glebov, R.N. and Kryzhanovskii, G.N., Ukr. Biokh. Zhurnal, 1983, E55, no. 4, pp. 460–474.

    Google Scholar 

  62. Reist, N.E., Buchanan, J., Li, J., DiAntonio, A., Buxton, E.M., and Schwarz, T.L., J. Neurosci., 1998, vol. 18, pp. 7662–7673.

    CAS  PubMed  Google Scholar 

  63. Pozzo-Miller, L.D., Gottschalk, W., Zhang, L., McDermott, K., Du, J., Gopalakrishnan, R., Oho, C., Sheng, Z.H., and Lu, B., J. Neurosci., 1999, vol. 19, pp. 4972–4983.

    CAS  PubMed  Google Scholar 

  64. Bykov, K.M., Vladimirov, G.E., Delov, V.E., Konradi, G.P., et al., Uchebnik fiziologii, Bykov, K.M., Ed., Moscow: MEDGIZ, 1955.

    Google Scholar 

  65. Semchenko, V.V. and Stepanov, S.S., Byul. Eksper. Biol. i Medic., 1986, vol. 102, no. 7, pp. 100–102.

    CAS  Google Scholar 

  66. Klau, M., Hartmann, M., Erdmann, K.S., Heumann, R., and Lessmann, V., J. Neurosci. Res., 2001, vol. 66, no. 3, pp. 327–336.

    Article  CAS  PubMed  Google Scholar 

  67. Wake, H., Moorhouse, A.J., Jinno, S., Kohsaka, S., and Nabekura, J., J. Neurosci., 2009, vol. 29, no. 13, pp. 3974–3980.

    Article  CAS  PubMed  Google Scholar 

  68. De Robertis, E., Pellegrino, De., Araldi, A., Rodrigues de Lores Arnaiz, G., and Salganicoff, L., J. Neurochem., 1962, vol. 9, pp. 23–35.

    Article  Google Scholar 

  69. Glebov, R.N. and Kryzhanovskii, G.N., Funktsional’naya biokhimiya sinapsov (Functional Biochemistry of Synapses), Moscow: Meditsina, 1978.

    Google Scholar 

  70. Alkondon, M. and Albuquerque, E.X., J. Neurophysiol., 2001, vol. 86, no. 6, pp. 3043–3055.

    CAS  PubMed  Google Scholar 

  71. Buhler, A.V. and Dunwiddie, T.V., Neuroscience, 2001, vol. 106, no. 1, pp. 55–67.

    Article  CAS  PubMed  Google Scholar 

  72. Son, J.H. and Winzer-Serhan, U.H., J. Comp. Neurol., 2008, vol. 511, no. 2, pp. 286–299.

    Article  CAS  PubMed  Google Scholar 

  73. Albuquerque, E.X., Pereira, E.F., Alkondon, M., and Rogers, S.W., Physiol. Rev., 2009, vol. 89, no. 1, pp. 73–120.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

    E. I. Zakharova, A. M. Dudchenko, M. M. Fedorova & E. L. Germanova

  2. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

    M. M. Svinov

  3. ul. Baltiiskaya 8, Moscow, 125315, Russia

    E. I. Zakharova

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  1. E. I. Zakharova
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  2. A. M. Dudchenko
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  3. M. M. Svinov
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  4. M. M. Fedorova
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  5. E. L. Germanova
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Correspondence to E. I. Zakharova.

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Original Russian Text © E.I. Zakharova, A.M. Dudchenko, M.M. Svinov, M.M. Fedorova, E.L. Germanova, 2010, published in Neirokhimiya, 2010, Vol. 27, No. 4, pp. 322–336.

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Zakharova, E.I., Dudchenko, A.M., Svinov, M.M. et al. Cholinergic systems of the rat brain and neuronal reorganization under conditions of acute hypoxia. Neurochem. J. 4, 290–303 (2010). https://doi.org/10.1134/S1819712410040082

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