Please use this identifier to cite or link to this item:
Title: Simvastatin Interferes With Process Outgrowth and Branching of Oligodendrocytes
Authors: SMOLDERS, Inge 
SMETS, Ilse 
MAIER, Olaf 
VAN DE VEN, Martin 
AMELOOT, Marcel 
Issue Date: 2010
Publisher: WILEY-LISS
Source: JOURNAL OF NEUROSCIENCE RESEARCH, 88 (15). p. 3361-3375
Abstract: Statins 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.
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.
Keywords: cholesterol; isoprenylation; morphology; multiple sclerosis; remyelination;cholesterol; isoprenylation; morphology; multiple sclerosis; remyelination
Document URI:
ISSN: 0360-4012
e-ISSN: 1097-4547
DOI: 10.1002/jor.22490
ISI #: 000283609900015
Category: A1
Type: Journal Contribution
Validations: ecoom 2011
Appears in Collections:Research publications

Show full item record


checked on Sep 3, 2020


checked on May 17, 2022

Page view(s)

checked on May 22, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.