Session: Current Topics in Biological Chemistry:

Multiple Sclerosis is characterized by immune-mediated myelin and axonal damage. The progression of the disease is connected to two fundamental processes: myelin destruction and failure to remyelinate, and continuous axonal damage with minute recovery potential. Currently, there are no FDA approved therapies that promote myelin repair. Therefore, investigating the molecular pathways underlying remyelination is crucial to developing new therapeutic strategies for promoting myelin repair and improving clinical results in people living with MS. Remyelination is mediated by oligodendrocyte progenitor cells (OPCs), which proliferate and differentiate into mature, myelinating oligodendrocytes. Several classes of nuclear hormone receptors (NRs) participate in regulating OPC differentiation and complex membrane formation in the CNS. In this work, I am systematically comparing the contribution of eight common NR ligands to myelination using an OPC differentiation assay. OPCs are isolated from six-day-old rat pups using an immunopanning technique and cells are differentiated in defined media with each NR ligand. Cells are immunostained with neuron-glial antigen- 2 (NG-2) for OPCs and myelin basic protein (MBP) for mature oligodendrocytes. The number of OPCs vs. oligodendrocytes are quantified and the morphology of the oligodendrocytes are assessed. Additionally, qPCR assays are performed to examine the expression levels of myelination-related genes: myelin Associated glycoprotein (mag), UDP-gallactose ceramide galactosyl transferase (cgt), and mbp in the different NR ligand treated cells. This data is used to identify the most efficient ligands for an RNAseq study to identify pathways that are activated during OPC differentiation that may provide insights into the remyelination process.

Dr Achala Punchi Hewage

Postdoctoral Researcher, University of Kansas

Appearances