Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(5): 3-10


I.F. Labunets, A.E. Rodnichenko, T.M. Panteleymonova

    State Institute of Genetic and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine


In young 129/Sv mice receiving neurotoxin cuprizone and thyroxin or estradiol we investigated the relationship between changes in behavioral indices and the number of neural stem cells, T-lymphocytes, microglia/macrophage cells in the brain assessed by nestin, CD3, Mac1 markers, as well as the number of latex phagocytic macrophages. Cuprizone was given with food daily for 3 weeks; L-thyroxin or β-estradiol were administered from the 8th day of the cuprizone diet, daily. It is shown that cuprizone significantly reduced motor, emotional and exploratory activities. Changes in behavioral indices coincided with an increase in the number of nestin+-, CD3+- and Mac1+-cells in the brain and active macrophages (1.6, 2.3, 1.5 and 1.2 times, respectively) comparing to the intact mice. In the thyroxin-treated mice the locomotor activity increased by 1.3 times, but it was lower comparing to the intact animals. І.Ф. Лабунець, А.Є. Родніченко, Т.М. Пантелеймонова Under the influence of thyroxin the number of nestin+-, Mac1+- cells and active macrophages decreased to the values of the intact group. After estradiol administration the locomotor and emotional activities increased 1.4 and 2.5 times, respectively, comparing to the cuprizone group. The number of nestin+-cells was higher in the group with estradiol than in the mice without it, while the number of active macrophages decreased and did not differ from the values of the intact group.Thus, in mice with the cuprizone demyelination model, the positive effect of thyroxin and estradiol on the CNS functioning was realized through the changes in the number of brain nestin+- cells and the factors of the pathology.

Keywords: сuprizone; thyroxin; estradiol; behavioral indices; neural stem cells; macrophages and T-lymphocytes, brain.


  1. Mishchenko TS, Shulga OD, Bobryk NV, Shulga LA. Multiple Sclerosis: Global Perspectives. Ukr Med ChasopisUkr Med J. 2014;101(3):84-7. [Ukrainian].
  3. Rybachuk O, Pivneva T. Contribution of neural stem cells to regeneration of the central nervous system. Int J Physiol Pathophysiol. 2014;5(1):83-96. CrossRef  
  4. El-Etr M., Ghoumari A., Sitruk-Ware R., Schumacher M. Hormonal influences in multiple sclerosis: New therapeutic benefits for steroids. Maturitas. 2011;68(1): 47-51. CrossRef PubMed
  6. Heidher RM, Emerson MR, Le Vine SM. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis. Neural Regen Res. 2017;12(8):1262-67. CrossRef PubMed PubMedCentral
  8. Praet J, Guglielmetti C, Berneman Z, Van der Linden, Ponsaerts P. Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis. J Neubiorev. 2014;47:485-505. CrossRef PubMed
  10. Gudi V, Gingele S, Skripuletz Th, Stangel M. Glial response during cuprizon-induced de- and remyelination in the CNS: lessons learned. Front Cell Neurosci. 2014;8 (Article 73): 24. CrossRef PubMed PubMedCentral
  12. Labunets I. F. Possibilities and prospects of the application of the in vivo and in vitro toxic cuprizone model for demyelination in experimental and clinical neurology (literature review and own research results). Ukr Neurol J. 2018;2:63-8. [Ukrainian]. CrossRef  
  13. Silvestroff L, Bartucci S, Pasquini J, Franco P. Cuprizoneinduced demyelination in the rat cerebral cortex and thyroid hormone effects on cortical remyelination. Exp Neurol. 2012;235(1):357-67. CrossRef PubMed
  15. Kipp M, Clarner T, Dang J, Copray S, Beyer C. The cuprizone animal model: new insights into an old story. Acta Neuropathol. 2009;118(6):723-36. CrossRef PubMed
  17. Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990; 60(4): 585-95. CrossRef  
  18. Labunets IF, Melnyk NO, Rodnichenko AE, Rymar SE, Utko NA.Cuprizone-induced disorders of central nervous system neurons, behavioral reactions, brain activity of macrophages and antioxidant enzymes in the mice of different ages: Role of leukemia inhibitory factor in their improvement. J Aging Geriat Med. 2017;1(2):1-8.
  20. Amikishieva AV. Behavioral phenothyping: up-to date methods and equipment. Vestnik VOGiS. 2009;13(3): 529-42. [Russian].
  22. Zhang M, Zhan XL, Mazi Y, Chen XS, Cai Qi Y, Yao Zh X. Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period. Exp Biol Med (Maywood). 2015; 240:1183-96. CrossRef PubMed PubMedCentral
  24. Calza L, Fernandez M, Giuliani A, Aloe L, Giardino L. Thyroid hormone activates oligodendrocyte precursors and increases a myelin-forming protein and NGF content in the spinal cord during experimental allergic encephalomyelitis. PNAS. 2002;99(5):3258-63. CrossRef PubMed PubMedCentral
  26. Gothie JD, Sebillot A, Luongo G, Legendre M, Nguyen Van C, La Blay K. et al. Adult neural stem cell fate is determined by thyroid hormone activation of mitochondrial metabolism. Mol. Metabolism. 2017;6:1551-61. CrossRef PubMed PubMedCentral
  28. Labunets I, Rodnichenko A, Melnyk N, Utko N. Neuroprotective effect of melatonin in mice with toxic cuprizone model of demyelination and possible ways of its realization. Cell and Organ Transplantology. 2018;6(2):145-51. CrossRef  
  29. Mancini A, Di Segni ChDi, Raimondo S, Olivieri G, Silvestrini A, Meucci E. et al. Thyroid hormones, oxidative stress, and inflammation. Mediators Inflammation. 2016; Article ID 6757154, 12. CrossRef PubMed PubMedCentral
  31. Okada M, Makino A, Nakajima M, Okuyama S, Furukawa Sh, Furukawa Y. Estrogen stimulates proliferation and differentiation of neural stem. progenitor cells through different signal transduction pathways. Int J Mol Sci. 2010;11:4114-23. CrossRef PubMed PubMedCentral
  33. Jiang F, Frederick TJ, Wood TL. IGF-1 sinergires with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle. Dev Biol. 2001;232:414-23. CrossRef PubMed
  35. Taylor LC, Puranam K, Gilmore W, Ting J.P-Y, Matsushima GK. !7-β estradiol protects male mice from cuprizone-induced demyelination and oligodendrocyte loss. Neurobiol Dis. 2010;39(2):127-37. CrossRef PubMed PubMedCentral
  37. Liubich LD, Lisyany ML. Immunobiological properties of neurogenic cells of the fetal brain. Immune responses to neurogenic stem cells in vitro and in vivo. Fiziol Zh. 2018;64(1):103-17. [Ukrainian]. CrossRef

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.