Role of Elongator in Central Nervous System Remyelination.
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1
University of Liège, GIGA Neurosciences, Belgium
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2
University of Liège, GIGA Signal Transduction, Belgium
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which subsequent remyelination can spontaneously take place but often fails or is incomplete, for yet unknown reasons. In order to better understand this failure, we are studying the role of the Elongator complex in the CNS demyelination and remyelination processes. Elongator is a highly conserved complex composed of 6 subunits (Elp1 to Elp6), Elp3 being the enzymatically active subunit through a lysine acetyltransferase activity, and it is involved in cell migration and tRNA modification.
We first engineered a new conditional knockout mouse (cKO) model (PLPCreERT2:Elp3floxed) in which Elp3 is specifically invalidated in the oligodendroglial lineage after tamoxifen treatment. We then compared wild type (WT) and cKO mice using the cuprizone model, a toxic experimental model of demyelination characterized by a reproducible demyelination in certain regions of the CNS followed by a spontaneous remyelination. Preliminary results seem to indicate that the recovery is improved and fastened in the cKO mice compared to the WT.
In parallel, we depleted Elp1 or Elp3 with shRNAs in an oligodendrocyte precursor cell line. We then compared their cAMP-induced differentiation by measuring the expression of myelin protein genes in control and in depleted cells. Our results show an increased expression of MAG and MOG in both Elp1 and Elp3 depleted cells.
Taken together, our results suggest that Elongator could act as a negative regulator of the remyelination. The next step of this project will be to elucidate the molecular pathways triggered by Elongator in this process.
Keywords:
Elongator,
oligodendrocyte precursor cell (OPC),
remyelination,
differentiation,
Multiple Sclerosis
Conference:
11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015.
Presentation Type:
Poster presentation
Topic:
Neuroscience
Citation:
Dion
V,
Boerboom
A,
Pieltain
A,
Chariot
A and
FRANZEN
R
(2015). Role of Elongator in Central Nervous System Remyelination..
Front. Neurosci.
Conference Abstract:
11th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2015.89.00026
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Received:
05 May 2015;
Published Online:
05 May 2015.
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Correspondence:
Miss. Valérie Dion, University of Liège, GIGA Neurosciences, Liège, Belgium, v.dion@ulg.ac.be