No abstract

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cells survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression.Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the neurodegenerative disorders pathogenesis and designing more effective treatments.

Astrocyte-secreted factors play multifunctional roles in central nervous system (CNS) in health and disease. Here, we examined the regulatory machinery of long non-coding RNAs (lncRNAs) on gene expression of several factors of great importance in remyelination - CNTF, NT-3, FGF2 and PDGF-C - in human astrocytoma cell line via in silico and experimental studies. To know any expression correlations among these genes as well as their changes in inflammatory conditions, their expression was measured under H2O2 induction. Using available databases, a computational screening was performed to collect lncRNAs having the potentiality of regulating expression of the target genes. MALAT1 and Lnc-DC were selected as high potential expression regulators of four genes of the study among 40 lncRNAs that were evaluated bioinformatically. Downregulation of remyelination-modulating genes of interest under DNAzyme-induced suppression of MALAT1 or Lnc-DC verified the regulatory role of these lncRNAs. More detailed information on expression regulatory machinery of lncRNAs and remyelination-modulating genes in inflammatory conditions could pave the way for understanding the reasons of their inefficiency in demyelinating diseases such as Multiple Sclerosis (MS).

Objective: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is expressed by neurons and glial cells in the central nervous system (CNS). In the CNS, BDNF is responsible for neuroprotection and neurogenesis. Recent studies showed that the Fingolimod, the first oral medicine for relapsing-remitting multiple sclerosis (RR-MS), induces BDNF expression. Besides, It is well demonstrated that long noncoding RNAs (lncRNAs) have a pivotal role in gene regulation. This study is mainly focused on how Fingolimod treatment plays role in BDNF regulation in coordination with lncRNAs. Methods: An in-silico study was performed to predict BDNF-regulatory candidate lncRNAs using online tools. Then, the expression of BDNF-related lncRNAs was analyzed in patients with relapsing-remitting multiple sclerosis (RRMS) at baseline and after three months of Fingolimod treatment. Results: Based on in silico results, two lncRNAs with potential regulatory functions on the BDNF including, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX Transcript Antisense RNA (HOTAIR), and also natural antisense of BDNF were selected. Fingolimod treatment increased the expression of HOTAIR lncRNA; however, the BDNF antisense RNA (BDNF-AS) expression was reduced dramatically. Furthermore, the results indicate a positive correlation between HOTAIR and MALAT1 lncRNAs and BDNF. Also, after Fingolimod treatment, the patients' EDSS scores were declined or remained unchanged, indicating disease hindrance by Fingolimod therapy. Conclusion: Altogether, fingolimod exerts protective roles in RRMS patients probably by the mediation of HOTIAR and BDNF-AS lncRNAs.

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cell survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression. Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments.