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

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. © 2024 Isfahan University of Medical Sciences(IUMS). All rights reserved.