Skip to main content
SpringerLink
Log in

Changes in the Content of Sphingolipids in the Nigrostriatal Dopaminergic System in the Brain of Mice with a Neurotoxic Model of Parkinson’s Disease

  • EXPERIMENTAL ARTICLES
  • Published:
Neurochemical Journal Aims and scope Submit manuscript

Abstract—It was shown that sphingolipids are necessary for the normal functioning of neurons, and disturbance of their metabolism accompanies the development of brain diseases, including Parkinson’s disease (PD). Since the possibilities for studying the role of sphingolipids in the pathogenesis of PD in patients are extremely limited, experimental models must be used to solve this problem. Thus, in this work, using chromatography-mass spectrometry, the content of key molecular species of sphingolipids, total ceramides, hexosylceramides, and their derivatives, sphingosine and sphinganine, with proapoptotic properties in mice were studied using a model of the clinical stage of PD for the first time. This model was obtained by systemically administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which in the brain turns into MPP +, a toxin for catecholaminergic neurons. In the control, instead of MPTP, 0.9% NaCl was injected. It was shown that the total concentration of all studied sphingolipids increases in the substantia nigra, the location of dopaminergic neuron bodies, compared to the control. This occurred due to an increase in the concentration of ceramides associated with fatty acids, such as C18:1/14:0, C18:1/18:0, C18:1/24:1, and monohexosylceramides associated with fatty acids such as C18:1/18:0 and C18:1/24:1. Unlike the substantia nigra, the striatum, the site of projection of dopaminergic axons, had no changes in the content of sphingolipids. These data indicate that the death of nigrostriatal dopaminergic neurons in the PD model is accompanied by a change in the metabolism of sphingolipids, which opens up new possibilities for studying their role in the pathogenesis of this disease and in the search for a new class of drugs that correct sphingolipid metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

REFERENCES

  1. Alessenko, A.V. and Albi, E., Front. Neurol., 2020, p. 11:437.

  2. Gutner, U.A., Shupik, M.A., Maloshitskaya, O.A., Sokolov, S.A., Rezvykh, A.P., Funikov, S.Y., Lebedev, A.T., Ustyugov, A.A., and Alessenko, A.V., Biochemistry (Mosc.), 2019, vol. 84, no. 10, pp. 1166–1176.

    Article  CAS  Google Scholar 

  3. Sardi, S.P., Viel, C., Clarke, J., Treleaven, C.M., and Richards, A.M., Proc. Natl. Acad. Sci. USA, 2017, vol. 114, no. 10, pp. 2699–2704.

    Article  CAS  Google Scholar 

  4. Wang, G. and Bieberich, E., Adv. Biol. Regul., 2018, vol. 70, pp. 51–64.

    Article  CAS  Google Scholar 

  5. Hannun, Y.A. and Obeid, L.M., Nat. Rev. Mol. Cell. Biol., 2008, vol. 9, no. 2, pp. 139–150.

    Article  CAS  Google Scholar 

  6. Maceyka, M. and Spiegel, S., Nature, 2014, vol. 510, pp. 58–67.

    Article  CAS  Google Scholar 

  7. Trayssac, M., Hannun, Y.A., and Obeid, L.M., J. Clin. Invest., 2018, vol. 128, no. 7, pp 2702–2712.

    Article  Google Scholar 

  8. Alecu, I. and Bennett, S., Front. Neurosci., 2019, vol. 13, pp. 328–332.

    Article  Google Scholar 

  9. Galvagnion, C., J. Parkinson’s Disease, 2017, vol. 7, pp. 433–450.

    Article  CAS  Google Scholar 

  10. Xicoy, H., Wieringa, B., and Martens, G.J., Cells, 2019, vol. 8, no. 1, pp. 27–33.

    Article  CAS  Google Scholar 

  11. Indellicato, R. and Trinchera, M., Int. J. Mol. Sci., 2019, vol. 20, p. E3304.

    Article  Google Scholar 

  12. Gegg, M.E. and Schapira, A.H.V., FEBS J., 2018, vol. 285, pp. 3591–3603.

    Article  CAS  Google Scholar 

  13. Rocha, E.M., Smith, G.A., Park, E., Cao, H., Graham, A.R., Brown, E., McLean, J.R., et al., Antioxid. Redox. Signal, 2015, vol. 23, no. 6, pp. 550–564.

    Article  CAS  Google Scholar 

  14. Mielke, M.M., Maetzler, W., Haughey, N.J., Bandaru, V.V., Savica, R., Deuschle, C., et al., PLoS One, 2013, vol. 8, no. 9, p. 73094.

    Article  Google Scholar 

  15. Bligh, T.G. and Dyer, W.J., Can. J. Biochem. Physiol, 1959, vol. 37, pp. 911–917.

    Article  CAS  Google Scholar 

  16. Hannun, Y.A. and Luberto, C., Trends. Cell. Biol., 2000, vol. 10, pp. 73–80.

    Article  CAS  Google Scholar 

  17. 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  Google Scholar 

  18. Kozina, E.A., Kim, A.R., Kurina, A.Y., and Ugrumov, M.V., Neurobiol. D., 2017, vol. 98, pp. 108–121.

    Article  CAS  Google Scholar 

  19. Kozina, E.A., Khakimova, G.R., Khaindrava, V.G., Kucheryanu, V.G., Vorobyeva, N.E., Krasnov, A.N., Georgieva, S.G., Kerkerian-Le, GoffL., and Ugrumov, M.V., J. Neurol. Sci., 2014, vol. 340, pp. 198–207.

    Article  CAS  Google Scholar 

  20. Mingazov, E.R., Khakimova, G.R., Kozina, E.A., Medvedev, A.E., Buneeva, O.A., Bazyan, A.S., and Ugrumov, M.V., Mol. Neurobiol., 2018, vol. 55, pp. 2991–3006.

    Article  CAS  Google Scholar 

  21. Kim, A., Nigmatullina, R., Zalyalova, Z., Soshnikova, N., Krasnov, A., Vorobyeva, N., Georgieva, S., Kudrin, V., Narkevich, V., and Ugrumov, M., Mol. Neurobiol., 2019, vol. 56, pp. 3437–3450.

    Article  CAS  Google Scholar 

  22. Nicotra, A. and Parvez, S., Neurotoxicol. Teratol., 2002, vol. 24, pp. 599–605.

    Article  CAS  Google Scholar 

  23. Jackson-Lewis, V., Jakowec, M., Burke, R.E., and Przedborski, T., Neurodegeneration, 1995, vol. 4, pp. 257–269.

    Article  CAS  Google Scholar 

  24. Agid, Y., Lancet, 1991, vol. 337, pp. 1321–1324.

    Article  CAS  Google Scholar 

  25. Krown, K.A., Page, M.T., Nguyen, C., Zechner, D., Gutierrez, V., Comstock, K.L., et al., J. Clin. Invest., 1996, vol. 98, pp. 2854–2865.

    Article  CAS  Google Scholar 

  26. Sweeney, E.A., Sakakura, C., Shirahama, T., Masamune, A., Ohta, H., Hakamori, S., and Igarashi, Y., Int. J. Cancer, 1996, vol. 66, pp. 358–366.

    Article  CAS  Google Scholar 

  27. Cuvillier, O., Nava, V.T., Murthy, S.K., Edsall, L.C., Levade, T., Milstien, S., and Spiegel, S., Cell Death Differ., 2001, vol. 8, pp. 162–171.

    Article  CAS  Google Scholar 

  28. Tamiya-Koizumi, K., Murate, T., Suzuki, M., Simbulan, C.M., Nakagawa, M., Takemura, M., et al., Biochem. Mol. Biol. Int., 1997, vol. 41, pp. 1179–1189.

    CAS  PubMed  Google Scholar 

  29. Taguchi, Y.V., Liu, J., Ruan, J., Pacheco, J., Zhang, X., Abbasi, J., et al., J. Neurosci., 2017, vol. 37, no. 40, pp. 9617–9631.

    Article  CAS  Google Scholar 

  30. Filippov, V., Song, M.A., Zhang, K., Vinters, H.V., Tung, S., Kirsch, W.M., Yang, J., and Duerksen-Hughes, P.J., J. Alzheimers. Dis., 2012, vol. 29, pp. 537–547.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the RFBR-KOMFI grant, project no. 18-00-01334.

Author information

Authors and Affiliations

  1. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 119334, Moscow, Russia

    A. V. Alessenko, M. A. Shupik, U. A. Gutner & O. A. Maloshitskaya

  2. Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia

    V. E. Blokhin & M. V. Ugrumov

  3. Moscow State University, Moscow, Russia

    A. T. Lebedev, O. A. Maloshitskaya & S. A. Sokolov

Authors
  1. A. V. Alessenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. E. Blokhin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. A. Shupik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U. A. Gutner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. T. Lebedev
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. O. A. Maloshitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. A. Sokolov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. V. Ugrumov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. V. Alessenko.

Ethics declarations

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

Ethical approval. All manipulations with animals were carried out in accordance with national and international requirements and rules approved by the Committee for the Protection of Animals of the Koltsov Institute of Developmental Biology of the Russian Academy of Sciences, protocol no. 27 from July 04, 2019.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alessenko, A.V., Blokhin, V.E., Shupik, M.A. et al. Changes in the Content of Sphingolipids in the Nigrostriatal Dopaminergic System in the Brain of Mice with a Neurotoxic Model of Parkinson’s Disease. Neurochem. J. 15, 175–180 (2021). https://doi.org/10.1134/S1819712421020021

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1819712421020021

Keywords:

Search

Navigation