Bulletin of Experimental Biology and Medicine

, Volume 168, Issue 3, pp 356–360 | Cite as

Specific Roles of JAKs and STAT3 in Functions of Neural Stem Cells and Committed Neuronal Progenitors during Ethanol-Induced Neurodegeneration

  • G. N. Zyuz’kovEmail author
  • L. A. Miroshnichenko
  • T. Yu. Polyakova
  • L. A. Stavrova
  • E. V. Simanina
  • V. V. Zhdanov

Peculiar roles of JAKs and STAT3 in realization of growth potential of various types of progenitor cells in neural tissue were examined during ethanol-induced neurodegeneration modeled both in vitro and in vivo. During in vitro action of C2H5OH, these signal molecules exerted the opposite effects on mitotic activity of multipotent neural stem cells and committed neural progenitors (the clonogenic PSA-NCAM+ cells). The JAKs and STAT3 inhibitors down-regulated the rate of neural stem cell division (proliferative activity) but up-regulated such activity of the committed neural progenitors. A long-term in vivo exposure of mice to ethanol inversed the roles of JAKs and STAT3 in determination of proliferative status of neural stem cells and eliminated involvement of JAKs in functional control over the committed progenitors of neurons. The data attest to much promise of STAT3 inhibitors in treatment of ethanol-induced CNS diseases as the remedies that stimulate realization of growth potential in multipotent neural stem cells and committed neural progenitors.

Key Words

ethanol-induced neurodegeneration neural stem cells JAKs STAT3 targeted therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zyuz’kov GN, Zhdanov VV, Udut EV, Miroshnichenko LA, Polyakova TY, Stavrova LA, Chaikovskii AV, Simanina EV, Minakova MY, Udut VV. Peculiarities of Intracellular Signal Transduction in the Regulation of Functions of Mesenchymal, Neural, and Hematopoietic Progenitor Cells. Bull. Exp. Biol. Med. 2019;167(2): 201-206. doi: CrossRefPubMedGoogle Scholar
  2. 2.
    Zyuz’kov GN, Miroshnichenko LA, Polyakova TY, Stavrova LA, Simanina EV, Agafonov VI, Udut EV, Zhdanov VV. Role of MAPK ERK1/2 and p38 in the Realization of Growth Potential of Various Types of Regeneration-Competent Cells in Mouse Neural Tissue during Ethanol-Induced Neurodegeneration In Vitro. Bull. Exp. Biol. Med. 2019;167(2):229-232. doi: CrossRefPubMedGoogle Scholar
  3. 3.
    Zyuzkov GN, Zhdanov VV, Danilets MG, Miroshnichenko LA, Udut EV, Dygaj AM. Patent RU No. 2599289. Tissue regeneration stimulating agent. Bull. No. 28. Published October 10, 2016.Google Scholar
  4. 4.
    Brust JC. Acute withdrawal: diagnosis and treatment. Handb. Clin. Neurol. 2014;125:123-131.CrossRefGoogle Scholar
  5. 5.
    Crews FT, Nixon K. Alcohol, neural stem cells, and adult neurogenesis. Alcohol Res. Health. 2003;27(2):197-204.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Jordaan GP, Emsley R. Alcohol-induced psychotic disorder: a review. Metab. Brain Dis. 2014;29(2):231-243.CrossRefGoogle Scholar
  7. 7.
    Nilsson M, Sonne C. Diagnostics and treatment of Wernicke— Korsakoff syndrome patients with an alcohol abuse. Ugeskr Laeger. 2013;175(14):942-944.PubMedGoogle Scholar
  8. 8.
    Nixon K. Alcohol and adult neurogenesis: roles in neurodegeneration and recovery in chronic alcoholism. Hippocampus. 2006;16(3):287-295.CrossRefGoogle Scholar
  9. 9.
    Seki T. Expression patterns of immature neuronal markers PSA-NCAM, CRMP-4 and NeuroD in the hippocampus of young adult and aged rodents. J. Neurosci. Res. 2002;70(3):327-334.CrossRefGoogle Scholar
  10. 10.
    Tateno M, Ukai W, Yamamoto M, Hashimoto E, Ikeda H, Saito T. The effect of ethanol on cell fate determination of neural stem cells. Alcohol Clin. Exp. Res. 2005;29(12, Suppl):225S-229S.CrossRefGoogle Scholar
  11. 11.
    Yang JY, Xue X, Tian H, Wang XX, Dong YX, Wang F, Zhao YN, Yao XC, Cui W, Wu CF. Role of microglia in ethanolinduced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages. Pharmacol. Ther. 2014;144(3):321-337.CrossRefGoogle Scholar
  12. 12.
    Zyuz’kov GN, Danilets MG, Ligacheva AA, Zhdanov VV, Udut EV, Miroshnichenko LA, Simanina EV, Chaikovskii AV, Trofimova ES, Minakova MY, Udut VV, Dygai AM. PI3K, MAPK EPK1/2 and p38 are involved in the realization of growth potential of mesenchymal progenitor cells under the influence of basic fibroblast growth factor. Bull. Exp. Biol. Med. 2014;157(4):436-439.CrossRefGoogle Scholar
  13. 13.
    Zyuz’kov GN, Miroshnichenko LA, Udut EV, Chaikovskii AV, Polyakova TY, Simanina EV, Stavrova LA, Agafonov VI, Zhdanov VV. Functional State of Various types of regenerationcompetent cells in the nervous tissue in ethanol-induced neurodegeneration. Bull. Exp. Biol. Med. 2019;166(3):317-320.CrossRefGoogle Scholar
  14. 14.
    Zyuz’kov GN, Udut EV, Miroshnichenko LA, Polyakova TY, Simanina EV, Stavrova LA, Prosekin GA, Zhdanov VV, Udut VV. Role of JAK/STAT3 signaling in functional stimulation of mesenchymal progenitor cells with alkaloid songorine. Bull. Exp. Biol. Med. 2018;165(5):665-668.CrossRefGoogle Scholar
  15. 15.
    Zyuz’kov GN, Zhdanov VV, Udut EV, Miroshnichenko LA, Polyakova TY, Stavrova LA, Udut VV. Strategy of pharmacological regulation of intracellular signal transduction in regeneration-competent cells. Bull. Exp. Biol. Med. 2019;166(4): 448-455.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • G. N. Zyuz’kov
    • 1
    Email author
  • L. A. Miroshnichenko
    • 1
  • T. Yu. Polyakova
    • 1
  • L. A. Stavrova
    • 1
  • E. V. Simanina
    • 1
  • V. V. Zhdanov
    • 1
  1. 1.E. D. Goldberg Research Institute of Pharmacology and Regenerative MedicineTomsk National Research Medical CenterTomskRussia

Personalised recommendations