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Neurochemical and Behavioral Features of Action of Pre-Fibrillar Oligomeric Structures of α-Sinuclein in Adult Mice

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Abstract—The pre-fibrillar oligomeric structures of the α-synuclein protein formed during misfolding play an important role in the molecular pathogenesis of Parkinson’s disease and other age-dependent neurodegenerative diseases. We studied the effect of toxic α-synuclein oligomers administered intranasally for 14 days on the motor activity, learning, memory, and anxiety of adult (6-month-old) male C57Bl/6 mice, and on the levels and metabolism of monoamines and neurotransmitter amino acids in the hippocampus and the frontal cortex. We used the open field, passive avoidance, and elevated plus maze tests. The levels of monoamines and their metabolites, and neurotransmitter amino acids in the brain tissue of animals were determined by high performance liquid chromatography with electrochemical detection. It was found that oligomers of α‑synuclein cause an increase in anxiety in adult mice, a pronounced decrease in dopamine levels and oppositely directed changes in dopamine metabolite levels in the hippocampus and frontal cortex. No significant changes were found in learning indices and long-term memory, motor activity of animals, levels of noradrenaline, serotonin, or neurotransmitter amino acids in the studied brain structures after treatment with α-synuclein oligomers. We compared the experimental data and the results of our previous studies on the behavioral and neurochemical effects of oligomeric protein structures in aging 12-month-old mice. The possible mechanisms of the age-dependent effects of the α-synuclein oligomers are discussed.

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REFERENCES

  1. Geht, A.B. and Popov, G.R., Medical and Social Aspects of Parkinson’s Disease. Parkinson’s Disease and Moving Disorder, M.: RKI Sovero Press, 2014, p. 450.

    Google Scholar 

  2. Chen, H., Burton, E.A., Ross, G.W., Huang, X., Savica, R., Abbott, R.D., Ascherio, A., Caviness, J.N., Gao, X., Gray, K.A., Hong, J.S., Kamel, F., Jennings, D., Kirshner, A., Lawler, C., Liu, R., Miller, G.W., Nussbaum, R., Peddada, S.D., Rick, A.C., Ritz, B., Siderowf, A.D., Tanner, C.M., Troster, A.I., and Zhang, J., Environ. Health Perspect., 2013, vol. 121, nos 11-12, pp. 1245–1252.

    Article  Google Scholar 

  3. Hindle, J.V., Age Ageing, 2010, vol. 39, no. 2, pp. 156–161.

    Article  Google Scholar 

  4. Borghammer, P., Mov. Disord., 2018, vol. 33, no. 1, pp. 48–57.

    Article  Google Scholar 

  5. Bridi, J.C. and Hirth, F., Front. Neurosci., 2018, vol. 19, p. 12.

    Google Scholar 

  6. Mehra, S., Sahay, S., and Maji, S.K., Biochim. Biophys. Acta. Proteins Proteom., 2019. https://doi.org/10.1016/j.bbapap.2019.03.001

  7. Gruden, M.A., Davidova, T.V., Yanamandra, K., Kucheryanu, V.G., Morozova-Roche, L.A., Sherstnev, V.V., and Sewell, R.D., Behav. Brain. Res., 2013, vol. 243, pp. 205–212.

    Article  CAS  Google Scholar 

  8. Gruden, M.A., Davydova, T.V., Narkevich, V.B., Fomina, V.G., Wang, C., Kudrin, V.S., Morozova-Roche, L.A., and Sewell, R.D., Behav. Brain. Res., 2014, vol. 263, pp. 158–168.

    Article  CAS  Google Scholar 

  9. Gruden, M.A. Davydova, T., V, Narkevich, V.B., Fomina, V.G., Wang, C., Kudrin, V.S., Morozova-Roche, L.A., and Sewell, R.D., Behav Brain. Res., 2015, vol. 279, pp. 191–201.

    Article  CAS  Google Scholar 

  10. Sherstnev, V.V., Kedrov, A.V., Solov’eva, O.A., Gruden’, M.A, Konovalova, E.V., Kalinin, I.A., and Proshin, A.T., Neurochem. J., 2017, vol. 11, no. 4, pp. 282–289.

    Article  CAS  Google Scholar 

  11. Gruden, M.A., Davydova, T.V., Kudrin, V.S., Wang, C., Narkevich, V.B., Morozova-Roche, L.A., and Sewell, R.D.E., ACS. Chem. Neurosci., 2018, vol. 9, no. 3, pp. 568–577.

    Article  CAS  Google Scholar 

  12. Roberts, H.L. and Brown, D.R., Biomolecules, 2015, vol. 5, pp. 282–305.

    Article  CAS  Google Scholar 

  13. Belujon, P. and Grace, A., Int. J. Neuropsychopharmacol., 2017, vol. 20, no. 12, pp. 1036–1046.

    Article  CAS  Google Scholar 

  14. Yang, W. and Yu, S., Cell Mol. Life. Sci., 2017, vol. 74, no. 8, pp. 1485–1501.

    Article  CAS  Google Scholar 

  15. Schoenfeld, T.J. and Cameron, H.A., Neuropsychopharmacology, 2015, vol. 40, no. 1, pp. 113–128.

    Article  Google Scholar 

  16. Schlachetzki, J.C., Grimm, T., Schlachetzki, Z., Ben Abdallah, N.M., Ettle, B., Vöhringer, P., Ferger, B., Winner, B., Nuber, S., and Winkler, J., J. Neurosci. Res., 2016, vol. 94, no. 1, pp. 62–73.

    Article  CAS  Google Scholar 

  17. Magen, I., Torres, E.R., Dinh, D., Chung, A., Masliah, E., and Chesselet, M.F., J. Parkinsons Dis., 2015, vol. 5, no. 3, pp. 669–680.

    Article  CAS  Google Scholar 

  18. Freichel, C., Neumann, M., Ballard, T., Müller, V., Woolley, M., Ozmen, L., Borroni, E., Kretzschmar, H.A., Haass, C., Spooren, W., and Kahle, P.J., Neurobiol. Aging, 2007, vol. 28, no. 9, pp. 1421–1435.

    Article  CAS  Google Scholar 

  19. Emamzadeh, F.N., J. Res. Med. Sci., 2016, vol. 9, pp. 21–29.

    Google Scholar 

  20. Kozina, E.A., Kolacheva, A.A., Kudrin, V.S., Kucheryanu, V.G., Khaindrava, V.G., and Ugryumov, M.V., Neurochem. J., 2016, vol. 10, no. 3, pp. 211–218.

    Article  Google Scholar 

  21. Kozina, E.A., Kim, A.R., Khakimova, G.R., and Ugryumov, M.V., Neurochem. J., 2016, vol. 10, no. 4, pp. 288–293.

    Article  CAS  Google Scholar 

  22. Gomazkov, O.A., Astrotsity–zvezdy, kotorye upravlyayut mozgom (Astrocytes—Stars That Control the Brain), Moscow: Izdatel’stvo IKAR, 2018.

  23. Bliederhaeuser, C., Grozdanov, V., and Speidel, A., Acta Neuropathol., 2016, vol. 131, no. 3, pp. 379–391.

  24. Couillard-Despres, S., Curr. Top. Behav. Neurosci., 2013, vol. 15, pp. 343–355.

    Article  CAS  Google Scholar 

  25. Le Grand, J.N., Gonzalez-Cano, L., Pavlou, M.A., and Schwamborn, J.C., Cell Mol. Life Sci., 2015, vol. 72, no. 4, pp. 773–797.

    Article  CAS  Google Scholar 

  26. Marxreiter, F., Regensburger, M., and Winkler, J., Cell Mol. Life Sci., 2013, vol. 70, no. 3, pp. 459–473.

    Article  CAS  Google Scholar 

  27. Calo, L., Wegrzynowicz, M., Santivanez-Perez, J., and Grazia Spillantini, M., Mov. Disord., 2016, vol. 31, no. 2, pp. 169–177.

    Article  CAS  Google Scholar 

  28. Benskey, M.J., Perez, R.G., and Manfredsson, F.P., J. Neurochem., 2016, vol. 137, no. 3, pp. 331–359.

    Article  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The authors are grateful to Professor Ludmilla Morozova-Roche, Department of Medical Biochemistry and Biophysics, Umeå University, Sweden for providing the native α-synuclein protein and technical support in obtaining the amyloidogenic structures of α-synuclein.

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No external funding was received.

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Authors and Affiliations

  1. Anokhin Institute of Normal Physiology, ul. Baltiiskaya 8, 125315, Moscow, Russia

    M. A. Gruden’, O. A. Solov’eva & V. V. Sherstnev

  2. Zakusov Istitute of Pharmacology, Moscow, Russia

    V. S. Kudrin & V. B. Narkevich

Authors
  1. M. A. Gruden’
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  2. O. A. Solov’eva
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  3. V. S. Kudrin
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  4. V. B. Narkevich
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  5. V. V. Sherstnev
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Correspondence to M. A. Gruden’.

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Conflict of interest. The authors declare that they have no conflict of interest.

Ethical approval. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Gruden’, M.A., Solov’eva, O.A., Kudrin, V.S. et al. Neurochemical and Behavioral Features of Action of Pre-Fibrillar Oligomeric Structures of α-Sinuclein in Adult Mice. Neurochem. J. 14, 25–31 (2020). https://doi.org/10.1134/S1819712420010092

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  • DOI: https://doi.org/10.1134/S1819712420010092

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