Effects of Valproic Acid in Preventing Cuprizone-Induced Oligodendrocyte Cell Death

Document Type : Original Article(s)

Authors

1 Assistant Professor, Clinical Research Development Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran

2 Assistant Professor, Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Oligodendrocyte apoptosis is one of the principal mechanisms in progressive myelin destruction and the development of neurological disabilities. The oligodendrocyte cell death is usually caused by local inflammation and the toxic effects of some environmental factors. Valproic acid can increase cell survival and differentiation due to its diverse antioxidant, anti-apoptotic, anti-inflammatory, and neuroprotective effects. In the present study, the effects of this compound were investigated in preventing oligodendrocyte cell death in the mouse brain corpus callosum.
Methods: In this study, 40 mice were randomly divided into four groups: control, sham, cuprizone, and valproic acid/cuprizone. To kill oligodendrocyte cells, 0.2% caprizone compound was used. In addition, the combination of valproic acid was used intraperitoneally, daily with a dose of 300 mg/kg, and for three weeks. immunohistochemical and real-time methods were used to investigate the specific markers of oligodendrocyte cells.
Findings: The results showed that the percentage of cells expressing Oligodendrocyte transcription factor (Olig2) and Myelin oligodendrocyte glycoprotein (Mog) markers increased significantly in the group that received valproic acid compared to the groups that received cuprisone (P < 0.05). Also, an increase in the expression of oligodendrocytes-specific genes was reported in the Real Time-PCR method.
Conclusion: The results of this study showed that valproic acid can prevent oligodendrocyte cell death, therefore, the use of this compound can be a suitable solution to prevent the destruction of myelin in nerve tissue

Highlights

Sahar Ghosouri: PubMed

Mitra Soleimani: Google Scholar, PubMed

Nazem Ghasemi: Google Scholar, PubMed

Keywords

Main Subjects

References

  1. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J 2017; 19(1): 1-10.
  2. Skaper SD. Neurotrophic factors: an overview. Methods Mol Biol 2018; 1727: 1-17.
  3. Romoli M, Mazzocchetti P, D'Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, et al. Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol 2019; 17(10): 926-46.
  4. Duan Q, Li S, Wen X, Sunnassee G, Chen J, Tan S, et al. Valproic acid enhances reprogramming efficiency and neuronal differentiation on small molecules staged-induction neural stem cells: suggested role of mTOR signaling. Front Neurosci 2019; 13: 867.
  5. Bebitoğlu BT, Oğuz E, Acet G. Effect of valproic acid on oxidative stress parameters of glutamate-induced excitotoxicity in SH-SY5Y cells. Exp Ther Med 2020; 20(2): 1321-8.
  6. Uzel G, Oylumlu E, Durmus L, Ciraci C. Duality of valproic acid effects on inflammation, oxidative stress and autophagy in human eosinophilic cells. Int J Mol Sci 2023; 24(17): 13446.
  7. Karimi Z, Zarifkar A, Dianatpour M, Mirzaei E, Dara M, Aligholi H. Nanosilibinin ameliorates anxiety, learning impairment and Wnt-β catenin related genes expression deficits in zebrafish model of Autism Spectrum Disorder. [Online]. [cited 2022 Aug 22]; Avilable from: URL:

https://assets.researchsquare.com/files/rs-1980576/v1/386b2575-e53a-48f8-aeda-6165775bff59.pdf?c=1663626571

  1. Liu Y, Hao S, Yang B, Fan Y, Qin X, Chen Y, et al. Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson’s disease model. Biochem Pharmacol 2017; 140: 115-23.
  2. Vallée A, Lecarpentier Y, Guillevin R, Vallée JN. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease. Acta Biochim Biophys Sin (Shanghai) 2017; 49(10): 853-66.
  3. Chen L, Cui X, Wu Z, Jia L, Yu Y, Zhou Q, et al. Transplantation of bone marrow mesenchymal stem cells pretreated with valproic acid in rats with an acute spinal cord injury. Biosci Trends 2014; 8(2): 111-9.
  4. 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.
  5. Azuchi Y, Kimura A, Guo X, Akiyama G, Noro T, Harada C, et al. Valproic acid and ASK1 deficiency ameliorate optic neuritis and neurodegeneration in an animal model of multiple sclerosis. Neurosci Lett 2017; 639: 82-7.
  6. 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.
  7. Mardani M, Ganji R, Ghasemi N, Kazemi M, Razavi S. Impact of intraventricular human adipose-derived stem cells transplantation with pregnenolone treatment on remyelination of corpus callosum in a rat model of multiple sclerosis. Cell J 2022; 24(12): 748-56.
  8. Vecera CM, Jones G, Chong AC, Ruiz AC, Rong C, Soares JC, et al. Intracellular signaling cascades in bipolar disorder. In: Machado-Vieira R, SoaresJ, editors. Biomarkers in bipolar disorders. Amsterdam, Netherlands: Elsevier Science; 2022. p. 31-47.
  9. Ghosouri S, Bakhtiari M, Mitra S, Ghasemi N. Valproic acid effects on human adipose-derived stem cell differentiation into oligodendrocytes and improved remyelination in a mouse model of Multiple Sclerosis. Int J Dev Biol 2023; 67(3):
    101-8.
  10. Trejo-Solis C, Escamilla-Ramirez A, Jimenez-Farfan D, Castillo-Rodriguez RA, Flores-Najera A, Cruz-Salgado A. Crosstalk of the Wnt/β-catenin signaling pathway in the induction of apoptosis on cancer cells. Pharmaceuticals (Basel) 2021; 14(9):
Journal of Isfahan Medical School
Volume 41, Issue 747
3rd Week, February
January and February 2024
Pages 1090-1095

Files

History

  • Receive Date: 12 November 2023
  • Revise Date: 21 February 2024
  • Accept Date: 24 February 2024

Share

How to cite

Statistics