title: Analysis of miRNA in Normal Appearing White Matter to Identify Altered CNS Pathways in Multiple Sclerosis.
abstract: Genetic studies suggest that the immune system is the greatest genetic contributor to multiple sclerosis (MS) susceptibility. Yet, these immune-related genes do not explain why inflammation is limited to the CNS in MS. We hypothesize that there is an underlying dysregulation in the CNS of MS patients that makes them more vulnerable to CNS inflammation. The sparsity of CNS-related genes associated with MS suggests that epigenetic changes in the CNS may play a role. Thus, a miRNA profiling study was performed in NAWM of MS patients and control subjects to determine if specific CNS pathways can be identified that may be altered due to miRNA-mediated post-transcriptional dysregulation. There were 15 differentially expressed miRNAs found in the MS patients' NAWM. Pathway analysis indicated that the MAPK pathway and pathways associated with the blood-brain barrier were predicted to be significantly affected by these miRNAs. Using target predication and mRNA analysis, an inverse relationship was found between miR-191 and BDNF, SOX4, FZD5 and WSB1. The pathway and target analysis of the MS-associated miRNAs suggests that MS patients' CNS is more prone to inflammation and less capable of repair, yet enriched in neuroprotective mechanisms.
authors.affiliation: Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Mireia
authors.initials: M
authors.lastname: Guerau-de-Arellano
authors.affiliation: Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Meisen
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT.; Department of Neurology, The Ohio State University Wexner MedicalCenter, Columbus, OH, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pitt
authors.affiliation: Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neurology, The Ohio State University Wexner MedicalCenter, Columbus, OH, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.affiliation: Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Lovett-Racke
keywords: Brain-derived neurotrophic factor; Multiple Sclerosis; miRNA