Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11454
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dc.contributor.authorSMOLDERS, Inge-
dc.contributor.authorSMETS, Ilse-
dc.contributor.authorMAIER, Olaf-
dc.contributor.authorVAN DE VEN, Martin-
dc.contributor.authorSTEELS, Paul-
dc.contributor.authorAMELOOT, Marcel-
dc.date.accessioned2011-01-06T18:05:44Z-
dc.date.availableNO_RESTRICTION-
dc.date.available2011-01-06T18:05:44Z-
dc.date.issued2010-
dc.identifier.citationJOURNAL OF NEUROSCIENCE RESEARCH, 88 (15). p. 3361-3375-
dc.identifier.issn0360-4012-
dc.identifier.urihttp://hdl.handle.net/1942/11454-
dc.description.abstractStatins have attracted interest as a treatment option for multiple sclerosis (MS) because of their pleiotropic antiinflammatory and immunomodulatory effects. However, contradictory results have been described when they are applied to oligodendrocytes (OLGs), the cell type predominantly affected in MS. In this study we focus on the in vitro effect of statins on process outgrowth in OLN-93 cells, a well-characterized OLG-derived cell line, and primary cultures of neonatal rat OLGs. Application of the lipophilic simvastatin, as low as 0.1-1 mu M, disturbs process formation of both cell types, leading to less ramified cells. We show that both protein isoprenylation and cholesterol synthesis are required for the normal differentiation of OLGs. It is further demonstrated that the expression of 2',3'-cyclic-nucleotide-3' phosphodiesterase (CNP) and tubulin is lowered, concomitant with a reduction of membrane-bound CNP as well as tubulin. Therefore, we propose that lack of isoprenylation of CNP could help to explain the altered morphological and biochemical differentiation state of treated OLGs. Moreover, expression of specific myelin markers, such as myelin basic protein, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein, was compromised after treatment. We conclude that simvastatin treatment has detrimental effects on OLG process outgrowth, the prior step in (re)myelination, thereby mortgaging long-term healing of MS lesions. (C) 2010 Wiley-Liss, Inc.-
dc.description.sponsorshipThe authors thank Prof. Dr. Richter-Landsberg (University of Oldenburg) for providing us with the OLN-93 cell line. We express our gratitude to Wilfried Leyssens, Gunter Tans, and Katrijn Vanschoenbeek for technical assistance during this work. O.M. received a grant from the Bijzonder Onderzoekfonds from UH. Support by IAP P6/27 Functional Supramolecular Systems (BELSPO) to MVDV and by the FWO-onderzoeksgemeenschap "Scanning and Wide Field Microscopy of (Bio)-organic Systems" is also thankfully acknowledged. We also gratefully acknowledge using ImageJ freeware (NIH, Bethesda, MD; Dr. W. Rasband: http://rsb.info.nih.gov/ij/plugins/lsm-reader.html) and the LSM Toolbox plugin (University of Strasbourg; Drs. J. Mutterer, Y. Krempp, and P. Pirrotte).-
dc.language.isoen-
dc.publisherWILEY-LISS-
dc.subject.othercholesterol; isoprenylation; morphology; multiple sclerosis; remyelination-
dc.subject.othercholesterol; isoprenylation; morphology; multiple sclerosis; remyelination-
dc.titleSimvastatin Interferes With Process Outgrowth and Branching of Oligodendrocytes-
dc.typeJournal Contribution-
dc.identifier.epage3375-
dc.identifier.issue15-
dc.identifier.spage3361-
dc.identifier.volume88-
local.format.pages15-
local.bibliographicCitation.jcatA1-
dc.description.notes[Smolders, Inge; Smets, Ilse; vandeVen, Martin; Steels, Paul; Ameloot, Marcel] Hasselt Univ, Sch Life Sci, Biomed Res Inst, Diepenbeek, Belgium. [Smolders, Inge; Smets, Ilse; vandeVen, Martin; Steels, Paul; Ameloot, Marcel] Transnat Univ Limburg, Diepenbeek, Belgium. [Smets, Ilse] PHL Univ Coll, Dept PHL Bio, Diepenbeek, Belgium. [Maier, Olaf] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Sect Membrane Cell Biol, A Groningen, Netherlands. [Maier, Olaf] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany. marcel.ameloot@uhasselt.be-
local.type.refereedRefereed-
local.type.specifiedArticle-
dc.bibliographicCitation.oldjcatA1-
dc.identifier.doi10.1002/jor.22490-
dc.identifier.isi000283609900015-
item.fulltextNo Fulltext-
item.validationecoom 2011-
item.contributorSMOLDERS, Inge-
item.contributorSTEELS, Paul-
item.contributorSMETS, Ilse-
item.contributorMAIER, Olaf-
item.contributorVAN DE VEN, Martin-
item.contributorAMELOOT, Marcel-
item.fullcitationSMOLDERS, Inge; SMETS, Ilse; MAIER, Olaf; VAN DE VEN, Martin; STEELS, Paul & AMELOOT, Marcel (2010) Simvastatin Interferes With Process Outgrowth and Branching of Oligodendrocytes. In: JOURNAL OF NEUROSCIENCE RESEARCH, 88 (15). p. 3361-3375.-
item.accessRightsClosed Access-
crisitem.journal.issn0360-4012-
crisitem.journal.eissn1097-4547-
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