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http://hdl.handle.net/1942/42291
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DC Field | Value | Language |
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dc.contributor.author | WILLEMS, Emily | - |
dc.contributor.author | SCHEPERS, Melissa | - |
dc.contributor.author | PICCART, Elisabeth | - |
dc.contributor.author | WOLFS, Esther | - |
dc.contributor.author | HELLINGS, Niels | - |
dc.contributor.author | Ait-Tihyaty, Maria | - |
dc.contributor.author | VANMIERLO, Tim | - |
dc.date.accessioned | 2024-02-01T08:53:56Z | - |
dc.date.available | 2024-02-01T08:53:56Z | - |
dc.date.issued | 2024 | - |
dc.date.submitted | 2024-02-01T08:07:29Z | - |
dc.identifier.citation | FASEB JOURNAL, 38 (2) (Art N° e23413) | - |
dc.identifier.uri | http://hdl.handle.net/1942/42291 | - |
dc.description.abstract | Sphingosine-1-phosphate receptor (S1PR) modulators are clinically used to treat relapse-remitting multiple sclerosis (MS) and the early phase of progressive MS when inflammation still prevails. In the periphery, S1PR modulators prevent lymphocyte egress from lymph nodes, hence hampering neuroinflammation. Recent findings suggest a role for S1PR modulation in remyelination. As the Gi alpha-coupled S1P1 subtype is the most prominently expressed S1PR in oligodendrocyte precursor cells (OPCs), selective modulation (functional antagonism) of S1P1 may have direct effects on OPC functionality. We hypothesized that functional antagonism of S1P1 by ponesimod induces remyelination by boosting OPC differentiation. In the cuprizone mouse model of demyelination, we found ponesimod to decrease the latency time of visual evoked potentials compared to vehicle conditions, which is indicative of functional remyelination. In addition, the Y maze spontaneous alternations test revealed that ponesimod reversed cuprizone-induced working memory deficits. Myelin basic protein (MBP) immunohistochemistry and transmission electron microscopy of the corpus callosum revealed an increase in myelination upon ponesimod treatment. Moreover, treatment with ponesimod alone or in combination with A971432, an S1P5 monoselective modulator, significantly increased primary mouse OPC differentiation based on O4 immunocytochemistry. In conclusion, S1P1 functional antagonism by ponesimod increases remyelination in the cuprizone model of demyelination and significantly increases OPC differentiation in vitro. Ponesimod reverses a cuprizone-induced working memory deficit, restores the cuprizone-induced delay in latency time of the optic pathway, and enhances remyelination after cuprizone intoxication in vivo. Furthermore, ponesimod enhances differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in vitro.image | - |
dc.description.sponsorship | Research funding was provided by Janssen Research & Development to Tim Vanmierlo. The authors thank Rewind Therapeutics for providing the visual evoked potential equipment. | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.rights | 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | - |
dc.subject.other | cuprizone | - |
dc.subject.other | multiple sclerosis | - |
dc.subject.other | oligodendrocyte precursor | - |
dc.subject.other | remyelination | - |
dc.subject.other | visual evoked potentials | - |
dc.title | The sphingosine-1-phosphate receptor 1 modulator ponesimod repairs cuprizone-induced demyelination and induces oligodendrocyte differentiation | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 2 | - |
dc.identifier.volume | 38 | - |
local.format.pages | 15 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Vanmierlo, T (corresponding author), Hasselt Univ, Biomed Res Inst, Fac Med & Life Sci, Dept Neurosci, Diepenbeek, Belgium. | - |
dc.description.notes | tim.vanmierlo@uhasselt.be | - |
local.publisher.place | 111 RIVER ST, HOBOKEN 07030-5774, NJ USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | e23413 | - |
dc.identifier.doi | 10.1096/fj.202301557RR | - |
dc.identifier.pmid | 38243760 | - |
dc.identifier.isi | 001145418800001 | - |
dc.contributor.orcid | Willems, Emily/0000-0001-7725-2896; Wolfs, Esther/0000-0001-9277-6524 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Willems, Emily; Schepers, Melissa; Piccart, Elisabeth; Vanmierlo, Tim] Hasselt Univ, Biomed Res Inst, Fac Med & Life Sci, Dept Neurosci, Diepenbeek, Belgium. | - |
local.description.affiliation | [Willems, Emily; Schepers, Melissa; Vanmierlo, Tim] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. | - |
local.description.affiliation | [Schepers, Melissa; Hellings, Niels; Vanmierlo, Tim] Univ MS Ctr UMSC Hasselt Pelt, Hasselt, Belgium. | - |
local.description.affiliation | [Wolfs, Esther] Hasselt Univ, Biomed Res Inst BIOMED, Dept Cardio & Organ Syst, Diepenbeek, Belgium. | - |
local.description.affiliation | [Hellings, Niels] Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Diepenbeek, Belgium. | - |
local.description.affiliation | [Ait-Tihyaty, Maria] Janssen Res & Dev LLC, Titusville, NJ USA. | - |
local.uhasselt.international | yes | - |
item.fullcitation | WILLEMS, Emily; SCHEPERS, Melissa; PICCART, Elisabeth; WOLFS, Esther; HELLINGS, Niels; Ait-Tihyaty, Maria & VANMIERLO, Tim (2024) The sphingosine-1-phosphate receptor 1 modulator ponesimod repairs cuprizone-induced demyelination and induces oligodendrocyte differentiation. In: FASEB JOURNAL, 38 (2) (Art N° e23413). | - |
item.contributor | WILLEMS, Emily | - |
item.contributor | SCHEPERS, Melissa | - |
item.contributor | PICCART, Elisabeth | - |
item.contributor | WOLFS, Esther | - |
item.contributor | HELLINGS, Niels | - |
item.contributor | Ait-Tihyaty, Maria | - |
item.contributor | VANMIERLO, Tim | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0892-6638 | - |
crisitem.journal.eissn | 1530-6860 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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The sphingosine‐1‐phosphate receptor 1 modulator ponesimod repairs cuprizone‐induced demyelination and .pdf | Published version | 6.6 MB | Adobe PDF | View/Open |
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