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The behavior and neurotransmitter contents in brain structures of rats with Alzheimer’s disease modeled by administration of Aβ25–35

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Abstract

We studied behavioral and neurochemical alterations that were induced by modeling of Alzheimer’s disease (AD) using bilateral intracerebroventricular administration of Aβ25–35 at a dose of 7.5 nmol in each ventricle. After 5.5 weeks, cognitive and psychoemotional alterations in the Morris spatial learning and Porsolt’s forced-swim tests were observed in rats with strong symptoms that are typical of AD. Measurement of the contents of monoamines and their metabolites in rat-brain structures was performed using the HPLC with the ECD method 1 day after the end of the tests. In the dorsal striatum, we found a decrease in the contents of metabolites of dopamine (DA), including homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methyltyramine (3-MT), and a decrease in the indices of DA utilization, including DOPAC/DA and HVA/DA, whereas the DA content was stable in this structure. In the nucleus accumbens (NA, ventral striatum), we found a decreased level of the HVA/DA ratio, which reflects the lower turnover of extracellular DA. We also found a lower turnover of serotonin (5-HT), which was seen as a decrease in the 5-hydroxyindolacetic acid (5-HIAA)/5-HT ratio, whereas the 5-HT content was elevated. In the hypothalamus, we revealed a significant decrease in the DA level and the levels of its metabolites, including 3-MT and HVA, and 5-HT turnover. We found that Aβ25–35 influenced the indices of amino-acidergic neurotransmission, which was reflected by the higher glutamate content in the striatum. Our data show that cerebral neurotransmitter systems, such as the tuberoinfundibular, mesolimbic, and nigrostrial dopaminergic and the striatal serotonergic and glutamatergic systems, are involved in pathophysiological mechanisms of the development of cognitive and psychoemotional impairments that occur in AD, as modeled by administration of Aβ25–35.

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References

  1. Khaindrava, V.G., Kudrin, V.S., Kucheryanu, V.G., Klodt, P.D., Bocharov, E.V., Nanaev, A.K., Kozina, E.A., Kryzhanovskii, G.N., Raevskii, K.S., and Ugryumov, M.V., Byull. Eksp. Biol. Med., 2010, vol. 150, no. 11, pp. 494–497.

    Google Scholar 

  2. Ugryumov, M.V., Kozina, E.A., Khaindrava, V.G., Kudrin, V.S., Kucheryanu, V.G., Klodt, P.D., Narkevich, V.B., Bocharov, E.V., Kryzhanovskii, G.N., and Raevskii, K.S., Tekhnologii Zhivykh Sistem, 2011, no. 8, pp. 3–13.

    Google Scholar 

  3. Joyce, J.N., Murray, A.M., Hurtig, H.I., Gottlieb, G.L., and Trojanowski, J., Neuropsychopharmacol., 1998, vol. 19, pp. 472–480.

    Article  CAS  Google Scholar 

  4. Tanaka, Y., Meguro, K., Yamaguchi, S., Ishii, H., Watanuki, S., Funaki, Y., Yamaguchi, K., Yamadori, A., Iwata, R., and Masatoshi, I., Ann. Nuclear Med., 2003, vol. 17, no. 7, pp. 567–573.

    Article  Google Scholar 

  5. Walker, Z., Costa, D.C., Walker, R.W., Shaw, K., Gacinovic, S., Stevens, T., Livingston, G., Ince, P., McKeith, I.G., and Katona, C.L., J. Neurol. Neurosurg. Psychiatry, 2002, vol. 73, pp. 134–140.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Holtzer, R., Scarmeas, N., Wegesin, D.J., Marilyn, A., Brandt, J., Dubois, B.O., Hadjigeorgiou, G.M., and Stern, Y., J. Am. Geriatr. Soc., 2005, vol. 53, pp. 2083–2089.

    Article  PubMed  Google Scholar 

  7. Zahodnea, L.B., Devanand, D.P., and Sterna, Y., J. Alzheimers Dis., 2013, vol. 34, pp. 851–860.

    Google Scholar 

  8. Shirayama, Y. and Chaki, S., Curr. Neuropharmacol., 2006, vol. 4, pp. 277–291.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Robinson, D.S., MD Primary Psychiatry, 2007, vol. 14, no. 35, pp. 21–23.

    Google Scholar 

  10. Hochstrasser, T., Hohsfield, L.A., Sperner-Unterweger, B., and Humpel, C., J. Neurosci. Res., 2012, vol. 91, pp. 83–94.

    PubMed  Google Scholar 

  11. Stuerenburg, H.J., Ganzer, S., and Muller-Thomsen, T., Neuroendocrinology Lett., 2004, vol. 25, no. 6, pp. 435–437.

    Google Scholar 

  12. Mura, E., Preda, S., Govoni, S., Lanni, C., Trabace, L., Grilli, M., Lagomarsino, F., Pittaluga, A., and Marchi, M., J. Alzheimers Dis., 2010, vol. 19, pp. 1041–1053.

    CAS  PubMed  Google Scholar 

  13. Gonzalo-Ruiz, A., Gonzalez, I., and Sanz-Anquela, J.M., J. Chem. Neuroanat., 2003, vol. 26, no. 3, pp. 153–169.

    Article  CAS  PubMed  Google Scholar 

  14. Voronina, T.A., Ostrovskaya, R.U., and Garibova, T.L., Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv (Guide on Preclinical Studies of Drugs), Moscow: Grif i K, 2012, part I.

    Google Scholar 

  15. Maurice, T., Lockhart, B.P., and Privat, A., Brain Res., 1996, vol. 706, pp. 181–193.

    Article  CAS  PubMed  Google Scholar 

  16. Stepanichev, M.Y., Zdobnova, I.M., Zarubenko, I.I., Moiseeva, Y.V., Lazareva, N.A., Onufriev, M.V., and Gulyaeva, N.V., Physiol. Behav., 2004, vol. 80, no. 5, pp. 647–655.

    Article  CAS  PubMed  Google Scholar 

  17. Bures, J., Petran, M., and Zachar, J., Electrophysiological methods in biological research, Prague: Publishing House of the Czechoslovak Academy of Sciences, 1960.

    Google Scholar 

  18. Yamaguchi, Y., Miyashita, H., Tsunekawa, H., Mouri, A., Kim, H.C., Saito, K., Matsuno, T., Kawashima, S., and Nabeshima, T., J. Pharmacol. Exp. Ther., 2006, vol. 317, no. 3, pp. 1079–1087.

    Article  CAS  PubMed  Google Scholar 

  19. Wang, C., Yang, X., Zhuo, Y., Zhou, H., Lin, H.B., Cheng, Y.F., Xu, J.P., and Zhang, H.T., Int. J. Neuropsychopharmacol., 2012, vol. 15, pp. 749–766.

    Article  CAS  PubMed  Google Scholar 

  20. Morris, R.G.M., J. Neurosci. Methods, 1984, vol. 11, pp. 47–60.

    Article  CAS  PubMed  Google Scholar 

  21. Yamada, K., Tanaka, T., Mamiya, T., Shiotani, T., Kameyama, T., and Nabeshima, T., Br. J. Pharmacol., 1999, vol. 126, pp. 235–244.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. D’Agostino, G., Russo, R., Avagliano, C., Cristiano, C., Meli, R., and Calignano, A., Neuropsychopharmacol., 2012, vol. 37, pp. 1784–1792.

    Article  Google Scholar 

  23. Porsolt, R.D., Bertin, A., Blavet, N., Deniel, M., and Jalfre, M., Eur. J. Pharmacol., 1979, vol. 57, pp. 201–210.

    Article  CAS  PubMed  Google Scholar 

  24. Miroshnichenko, I.I., Kudrin, V.S., and Raevskii, K.S., Farmakol. Toksikol., 1988, vol. 2, pp. 26–29.

    Google Scholar 

  25. Pearson, S.J., Czudek, C., Mercer, K., and Reynolds, G.P., J. Neural. Transm. Gen. Sect., 1991, vol. 86, no. 2, pp. 151–157.

    Article  CAS  PubMed  Google Scholar 

  26. Perez, S.E., Lazarov, O., Koprich, J.B., Chen, E., Rodriguez-Menendez, V., Lipton, J.W., Sisodia, S.S., and Mufson, E.J., J. Neurosci., 2005, vol. 25, no. 44, pp. 10220–10229.

    Article  CAS  PubMed  Google Scholar 

  27. Li, J., Zhu, M., Manning-Bog, A.B., Dimonte D.A., and Fink A.L., FASEB J., 2004, vol. 18, pp. 962–964.

    Article  CAS  PubMed  Google Scholar 

  28. Calabresi, P., Centonze, D., Gubellini, P., Pisani, A., and Bernardi, G., Trends Neurosci., 2000, vol. 23, pp. 120–126.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang, L., Zhou, F., and Dani, J.A., Mol. Pharmacol., 2004, vol. 66, pp. 538–544.

    Article  CAS  PubMed  Google Scholar 

  30. Olney, J.W., Labruyere, J., and Price, M.T., Science, 1989, vol. 244, pp. 1360–1362.

    Article  CAS  PubMed  Google Scholar 

  31. Masliah, E., Alford, M., Mallory, M., Rockenstein, E., Moechars, D., and Van Leuven, F., Exp. Neurol., 2000, vol. 163, pp. 381–387.

    Article  CAS  PubMed  Google Scholar 

  32. Olabarria, M., Noristani, H.N., Verkhratsky, A., and Rodríguez, J.J., Glia, 2010, vol. 58, pp. 831–38.

    PubMed  Google Scholar 

  33. Bobich, J.A., Zheng, Q., and Campbell, A., J. Alzheimers Dis., 2004, vol. 6, pp. 242–255.

    Google Scholar 

  34. Maragakis, N.J. and Rothstein, J.D., Nat. Clin. Prac. Neurol., 2006, vol. 2, pp. 679–689.

    Article  CAS  Google Scholar 

  35. Danysz, W. and Parsons, C.G., Br. J. Pharmacol., 2012, vol. 167, no. 2, pp. 324–352.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Medina, A.C., Charles, J.R., Espinoza-González, V., Sánchez-Resendis, O., Prado-Alcalá, R.A., Roozendaal, B., and Quirarte, G.L., Learn. Mem., 2007, no. 14, pp. 673–677.

    Google Scholar 

  37. Krupa, A.K., The UCLA USJ, 2009, vol. 22, pp. 39–46.

    Google Scholar 

  38. Scimeca, J.M. and Badre, D., Neuron, 2012, vol. 75, pp. 380–392.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Pazini, A.M., Gomes, G.M., Villarinho, J.G., da Cunha, C., Pinheiro, F., Ferreira, A.P., Mello, C.F., Ferreira, J., and Rubin, M.A., Neurochem. Res., 2013, vol. 38, no. 11, pp. 2287–2294.

    Article  CAS  PubMed  Google Scholar 

  40. Nestler, E.J. and Carlezon, W.A., J. Biol. Psychiatry, 2006, vol. 59, no. 12, pp. 1151–1159.

    Article  CAS  Google Scholar 

  41. Zangen, A., Overstreet, D.H., and Yadid, G., J. Neurochem., 1997, vol. 69, pp. 2477–2483.

    Article  CAS  PubMed  Google Scholar 

  42. Nocjar, C., Zhang, J., and Panksepp, J., Neuroscience, 2012, vol. 218, pp. 138–153.

    Article  CAS  PubMed  Google Scholar 

  43. Ring, R.M. and Regan, C.M., J. Psychopharmacol., 2013, vol. 66, pp. 538–544.

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Psychopharmacology and Laboratory of Neurochemical Pharmacology, Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia

    S. A. Litvinova, P. M. Klodt, V. S. Kudrin, V. B. Narkevich & T. A. Voronina

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  1. S. A. Litvinova
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  2. P. M. Klodt
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  3. V. S. Kudrin
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  4. V. B. Narkevich
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  5. T. A. Voronina
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Correspondence to S. A. Litvinova.

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Original Russian Text © S.A. Litvinova, P.M. Klodt, V.S. Kudrin, V.B. Narkevich, T.A. Voronina, 2015, published in Neirokhimiya, 2015, Vol. 32, No. 1, pp. 48–56.

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Litvinova, S.A., Klodt, P.M., Kudrin, V.S. et al. The behavior and neurotransmitter contents in brain structures of rats with Alzheimer’s disease modeled by administration of Aβ25–35 . Neurochem. J. 9, 39–46 (2015). https://doi.org/10.1134/S1819712415010055

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