Hotair and Malat1 Long Noncoding Rnas Regulate Bdnf Expression and Oligodendrocyte Precursor Cell Differentiation Publisher Pubmed



Khanihabibabadi F¹ ; Zare L² ; Sahraian MA³ ; Javan M² ; Behmanesh M¹ Show Affiliations
Source: Molecular Neurobiology Published:2022

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophins family with well-known roles in neural development, differentiation, survival, and synaptic plasticity; however, it has not been explained thoroughly how the expression of this critical gene is regulated. To reveal some aspects of Bdnf gene regulation, here it was explored whether metastasis-associated lung adenocarcinoma transcript 1 (Malat1) and HOX transcript antisense RNA (Hotair) lncRNAs play roles in the regulation of Bdnf expression level, the effect of fingolimod treatment on downstream pathways, and oligodendrocyte precursor cell (OPC) maturation. First, in rat primary glial culture, the effect of Hotair and Malat1 was investigated on Bdnf expression using downregulation by specific DNAzymes. Then, immunostaining and RT-qPCR assays were employed to assess the functions of fingolimod and lncRNAs on OPC maturation. The results demonstrated that Bdnf was significantly correlated to Hotair and Malat1 lncRNAs in glial cells. Also, a strong correlation was observed between these two lncRNAs in glial culture and isolated OPCs. Fingolimod treatment coordinated lncRNAs' role on Bdnf expression in glial cells and enhanced OPC myelination three times compared to control. Furthermore, results suggested that Malat1 may have a role in the last stages of the intrinsic oligodendrocyte (OL) myelination regardless of fingolimod treatment. As BDNF is involved in brain development, survival, and functions, understanding the regulatory mechanism behind BDNF expression leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.