Skip to main content
SpringerLink
Log in

GK-2 Reduces Death of Cultured Granule Neurons in Cerebellum Induced by the Toxic Effects of Zinc Ions

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Peptide mimetic of nerve growth factor GK-2 in a dose of 1-2 mg/liter improves survival of cultured rat cerebellar granule neurons exposed to the cytotoxic effect of zinc ions, but has no protective effect against copper ion cytotoxicity. Experiments on cultured rat hippocampal slices demonstrated that GK-2 did not affect reactivity of pyramidal neurons and long-term potentiation in the hippocampal field CA1 and the probability of glutamate release from presynaptic terminals in the synapses of the CA3-CA1 fields. The results suggest that GK-2 does not affect the functional properties of synaptic transmission under normal conditions, but protects neurons from the toxic effects of zinc, which creates prerequisites for GK-12 use in the treatment of neurodegenerative diseases.

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

Similar content being viewed by others

References

  1. Antipova TA. Neuroprotective effect of low-molecular peptide mimetic (GK-2) of nerve growth factor is related to activated synthesis of heat shock proteins (HSP32 and HSP70) and increased phosphorylation of TrkA receptor. Eksp. Klin. Farmakol. 2010;73(12):6-8. Russian.

  2. Antipova TA, Gudasheva TA, Seredenin SB. In vitro study of neuroprotective properties of GK-2, a new original nerve growth factor mimetic. Bull. Exp. Biol. Med. 2011;150(5):607-609.

    Article  CAS  PubMed  Google Scholar 

  3. Karpukhina OV, Inozemtsev AN, Gumargalieva KZ, Povarnina PYu, Gudasheva TA. Cytoprotective properties of the nerve growth factor and brain derived neurotrophic factor dipeptidic mimetics, GK-2 AND GSB-106, in the model of oxidative stress in paramecium caudatum. Farmakokinetika Farmakodinamika. 2018;(4):37-41. Russian.

  4. Seredenin SB, Gudasheva TA. The development of a pharmacologically active low-molecular mimetic of the nerve growth factor. Zh. Nevrol. Psikhiatr. 2015;115(6):63-70. Russian.

  5. Seredenin SB, Silachev DN, Gudasheva TA, Pirogov YA, Isaev NK. Neuroprotective effect of GK-2, a dipeptide mimetic of nerve growth factor, during experimental focal ischemia in middle cerebral artery basin. Bull. Exp. Biol. Med. 2011;151(5):584-587.

    Article  CAS  PubMed  Google Scholar 

  6. Stelmashook EV, Genrikhs EE, Mukhaleva EV, Kapkaeva MR, Kondratenko RV, Skrebitsky VG, Isaev NK. Neuroprotective Effects of Methylene Blue In Vivo and In Vitro. Bull. Exp. Biol. Med. 2019;167(4):455-459. doi: https://doi.org/10.1007/s10517-019-04548-3

  7. Blakemore LJ, Trombley PQ. Zinc as a Neuromodulator in the Central Nervous System with a Focus on the Olfactory Bulb. Front. Cell. Neurosci. 2017;11:297. doi: https://doi.org/10.3389/fncel.2017.00297

  8. Genrikhs EE, Voronkov DN, Kapkaeva MR, Gudasheva TA, Glibka YA, Isaev NK, Stelmashook EV. The delayed protective effect of GK-2, а dipeptide mimetic of Nerve Growth Factor, in a model of rat traumatic brain injury. Brain Res. Bull. 2018;140:148-153. doi: https://doi.org/10.1016/j.brainresbull.2018.05.002

    Article  CAS  PubMed  Google Scholar 

  9. Isaev NK, Stelmashook EV, Genrikhs EE. Role of Nerve Growth Factor in Plasticity of Forebrain Cholinergic Neurons. Biochemistry (Mosc.). 2017;82(3):291-300.

    Article  CAS  PubMed  Google Scholar 

  10. Morley SN, Power JM, Coulson EJ, Bartlett PF. Zinc-mediated neuronal death is dependent on Trk activation. Exp. Neurol. 2007;205(2):360-366.

    Article  CAS  PubMed  Google Scholar 

  11. Stelmashook EV, Genrikhs EE, Kapkaeva MR, Zelenova EA, Isaev NK. N-Acetyl-L-cysteine in the Presence of Cu2+ Induces Oxidative Stress and Death of Granule Neurons in Dissociated Cultures of Rat Cerebellum. Biochemistry (Mosc). 2017;82(10):1176-1182.

    Article  CAS  PubMed  Google Scholar 

  12. Stelmashook EV, Genrikhs EE, Novikova SV, Barskov IV, Gudasheva TA, Seredenin SB, Khaspekov LG, Isaev NK. Behavioral effect of dipeptide NGF mimetic GK-2 in an in vivo model of rat traumatic brain injury and its neuroprotective and regenerative properties in vitro. Int. J. Neurosci. 2015;125(5):375-379.

    Article  CAS  PubMed  Google Scholar 

  13. Tidball P, Burn HV, Teh KL, Volianskis A, Collingridge GL, Fitzjohn SM. Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor- dependent synaptic and intrinsic plasticity. Brain Neurosci. Adv. 2017;1(1). doi: 10.1177/2398212816689792

Download references

Author information

Authors and Affiliations

  1. Research Center of Neurology, Moscow, Russia

    E. V. Stelmashook, O. P. Aleksandrova, P. D. Rogozin, E. E. Genrikhs, S. V. Novikova, I. N. Sharonova, V. G. Skrebitsky & N. K. Isaev

  2. V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia

    T. A. Gudasheva

  3. M. V. Lomonosov Moscow State University, Moscow, Russia

    N. K. Isaev

Authors
  1. E. V. Stelmashook
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. P. Aleksandrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. D. Rogozin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. E. Genrikhs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. V. Novikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. A. Gudasheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. N. Sharonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V. G. Skrebitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. K. Isaev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. K. Isaev.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stelmashook, E.V., Aleksandrova, O.P., Rogozin, P.D. et al. GK-2 Reduces Death of Cultured Granule Neurons in Cerebellum Induced by the Toxic Effects of Zinc Ions. Bull Exp Biol Med 168, 474–478 (2020). https://doi.org/10.1007/s10517-020-04734-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-020-04734-8

Key Words

Search

Navigation