Journal of Isfahan Medical School

Journal of Isfahan Medical School

Effects of Glycogen Synthase Kinase 3β Inhibitor on the Prevention of Oligodendrocyte Cell Death Induced by Cuprizone in Mouse Brain

Document Type : Original Article(s)

Authors
Sahar Ghosouri 1
Mitra Soleimani 2
Nazem Ghasemi 3
1 PhD Student, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Associate Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
10.48305/jims.v41.i730.0652
Abstract
Background: Many environmental factors are involved in the death of oligodendrocyte cells, myelin tissue destruction, and disturbance in the central nervous system function. The protective role of lithium chloride as a Glycogen synthase kinase 3β (GSK3-β) inhibitor has been proven in some neurological diseases. In the present study, the effects of this compound were investigated in the prevention of oligodendrocytes death in mouse brains.
Methods: In the present study, 40 female C57BL/6 mice weighing 20-25 grams were randomly divided into four groups: control, sham, cuprizone, and lithium chloride/cuprizone. Lithium chloride compound was used intra peritoneally daily. At the end of the study, in order to check the results, immunohistochemistry and Real-time PCR were used.
Findings: The results of immunohistochemistry staining showed that the percentage of cells that expressed Oligodendrocyte transcription factor (Olig2) and Myelin oligodendrocyte glycoprotein (Mog) markers increased significantly in the group that received lithium compared to the groups that received cuprizone (P < 0.05). In addition, Real-Time PCR results showed that the use of lithium can increase the expression of oligodendrocytes- specific genes.
Conclusion: The results of the present study showed that lithium chloride has the ability to prevent the oligodendrocytes death, and therefore, the use of this compound can be a suitable solution for preventing and reducing the progression of diseases that destroy central nervous tissue.
Keywords
Lithium chloride
Oligodendroglia
Oligodendrocyte Transcription Factor 2
Myelin-Oligodendrocyte Glycoprotein
Subjects
  1. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 2006; 19(1): 80-94.
  2. O’Gorman C, Bukhari W, Todd A, Freeman S, Broadley S. Smoking increases the risk of multiple sclerosis in Queensland, Australia. J Clin Neurosci 2014; 21(10): 1730-3.
  3. Speer G. Impact of vitamin D in neurological diseases and neurorehabilitation: from dementia to multiple sclerosis. Part I: the role of vitamin D in the prevention and treatment of multiple sclerosis [in
    Hungarian]. Ideggyogy Sz 2013; 66(9-10): 293-303.
  4. Bäärnhielm M, Olsson T, Alfredsson L. Fatty fish intake is associated with decreased occurrence of multiple sclerosis. Mult Scler 2014; 20(6): 726-32.
  5. Sloka S, Silva C, Pryse-Phillips W, Patten S, Metz L, Yong VW. A quantitative analysis of suspected environmental causes of MS. Can J Neurol Sci 2011; 38(1): 98-105.
  6. Chung WS, Lin CL, Kao CH. Carbon monoxide poisoning and risk of deep vein thrombosis and pulmonary embolism: a nationwide retrospective cohort J Epidemiol Community Health 2015; 69(6): 557-62.
  7. Hesse A, Wagner M, Held J, Brück W, Salinas-Riester G, Hao Z, et al. In toxic demyelination oligodendroglial cell death occurs early and is FAS independent. Neurobiol Dis 2010; 37(2): 362-9.
  8. Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Zarkesh Esfahani SH. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 2015; 4: 53.
  9. Soleimani M, Ghasemi N. Lithium chloride can induce differentiation of human immortalized RenVm cells into dopaminergic neurons. Avicenna J Med Biotechnol 2017; 9(4): 176-80.
  10. Gu XK, Li XR, Lu ML, Xu H. Lithium promotes proliferation and suppresses migration of Schwann cells. Neural Regen Res 2020; 15(10): 1955-61.
  11. Ghosouri S, Soleimani M, Bakhtiari M, Ghasemi N. Evaluation of in vivo lithium chloride effects as a GSK3-β inhibitor on human adipose derived stem cells differentiation into oligodendrocytes and re-myelination in an animal model of multiple sclerosis. Mol Biol Rep 2023; 50(2): 1617-25.
  12. Bakhtiari M, Ghasemi N, Salehi H, Amirpour N, Kazemi M, Mardani M. Evaluation of Edaravone effects on the differentiation of human adipose derived stem cells into oligodendrocyte cells in multiple sclerosis disease in rats. Life Sci 2021; 282: 119812.
  13. Makoukji J, Belle M, Meffre D, Stassart R, Grenier J, Shackleford GG, et al. Lithium enhances remyelination of peripheral nerves. Proc Natl Acad Sci U S A 2012; 109(10): 3973-8.
  14. Ahn M, Kim J, Park C, Cho J, Jee Y, Jung K, et al. Potential involvement of glycogen synthase kinase (GSK)-3β in a rat model of multiple sclerosis: evidenced by lithium treatment. Anat Cell Biol 2017; 50(1): 48-59.
Journal of Isfahan Medical School
Volume 41, Issue 730
2nd Week, October
September and October 2023
Pages 652-657

  • Receive Date 02 July 2023
  • Accept Date 29 July 2023