Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/42879
Title: | EAAT3 modulation of the oligodendrocyte lineage in in vitro and in vivo models of Multiple Sclerosis | Authors: | VAN VEGGEL, Lieve SCHEPERS, Melissa TIANE, Assia ROMBAUT, Ben Royakkers, J. Dilien , H. HELLINGS, Niels Moya, P. Schreiber, R. VANMIERLO, Tim |
Issue Date: | 2023 | Publisher: | WILEY | Source: | GLIA, 71 (S1) , p. E721 | Abstract: | Multiple sclerosis is the most common neurodegenerative disorder among adolescents, with 2.5 million people suffering worldwide. When the disease progresses, demyelination due to oligodendrocyte damage leads to neurodegeneration. The eventual inability to recover from this damage is in part due to the vulnerability of oligodendrocyte precursor cells (OPCs) to oxidative stress. No treatment is yet available to target the progression of disease. In this project we aim to protect OPCs from oxidative stress to sustain endogenous remyelination processes. We hypothesise that activation of the excitatory amino acid transporter 3 (EAAT3) in OPCs holds the key to protection from inflammation-induced oxidative stress. EAAT3 is a cysteine transporter, providing the cell with the rate limiting building block for glutathione (GSH) synthesis, the key antioxidant compromised in OPCs. We aim to confirm and elucidate the role of EAAT3 in OPC differentiation and myelination in vitro. The effect of EAAT3 modulation was investigated in the context of OPC differentiation (in vitro) and remyelination in the EAE model (in vivo). Immunohistochemistry was performed to determine the effects of EAAT3 inhibition and lentiviral overexpression on differentiation (MBP and O4). During the chronic EAE, visual evoked potentials (VEPs, both amplitude and latency) were measured to determine effects on de-and remyelination on comparison with vehicle and a positive control, riluzole. Cysteine presence and uptake is crucial for the viability and normal functioning of primary OPCs in vitro. Inhibition of EAAT3 decreased the capacity of OPCs to undergo differentiation. These findings provide a rationale to investigate whether activation/overexpression of EAAT3 might prove beneficial for OPC differentiation and thus remyelination. | Document URI: | http://hdl.handle.net/1942/42879 | ISSN: | 0894-1491 | e-ISSN: | 1098-1136 | ISI #: | 001191372500600 | Category: | M | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Poster Presentations.pdf | Published version | 436.3 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.