Iranian Journal of Medical Sciences
Iranian Journal of Medical Sciences

9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways

Document Type : Original Article(s)

Authors

Saeedeh Saeb 1
Hassan Azari 2
Zohreh Mostafavi-Pour 1
Amir Ghanbari 3
Sepideh Ebrahimi 1
Pooneh Mokarram 1

1 Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran;

2 Neural Stem Cell and Regenerative Neuroscience Laboratory, Department of Anatomical Sciences and Shiraz Stem Cell Institute, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Anatomical Sciences, Yasuj University of Medical sciences, Yasuj, Iran

https://doi.org/10.30476/ijms.2018.40573
Abstract
Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.Methods: Cortical neural stem cells were isolated from 14-day-old rat embryos and cultured using the neurosphere assay. The cells were treated in 4 different conditions for 1 week: the negative control group received only the basic fibroblast growth factor, the positive control group received only T3 without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3 group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on the level of the myelin basic protein (MBP) and the gene expression of the SOX10, MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than 0.05 was considered significant. Results: The mRNA expressions of the SOX10, MBP, and MBP gene were significantly increased in the treated groups compared with the negative control group; the increase was similar in the 9-cis-RA group and the positive control group. Furthermore, 9-cis-RA significantly decreased the expression of the HES5 gene, a Notch signaling pathway transcription factor, and 1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt signaling pathway co-receptor. Conclusion: It seems that 9-cis-RA and 1,25(OH)2D3 are good candidates to improve the differentiation of OPCs into oligodendrocytes.

Keywords

Cell differentiation
Oligodendrocyte precursor cells
9-cis-retinoic acid
1,25-dihydroxy vitamin D3
Receptors, Wnt
Notch signaling pathway
Iranian Journal of Medical Sciences
Volume 43, Issue 5 - Serial Number 5
95
September 2018
Pages 523-532


  • Received 21 June 2017
  • Revised 15 March 2020
  • Accepted 24 December 2018

Home

Guide for Authors

Submit Manuscript

Guide for Reviewers

Forms

News

Contact Us

FAQ

Suggestion and Complain