| Simvastatin interferes with process outgrowth and branching of oligodendrocytes. | |
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MedLine Citation:
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PMID: 20857509 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 μM, 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. |
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Authors:
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Inge Smolders; Ilse Smets; Olaf Maier; Martin vandeVen; Paul Steels; Marcel Ameloot |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neuroscience research Volume: 88 ISSN: 1097-4547 ISO Abbreviation: J. Neurosci. Res. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-12 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: United States |
Other Details:
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Languages: eng Pagination: 3361-75 Citation Subset: IM |
Affiliation:
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Biomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, Diepenbeek, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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2',3'-Cyclic-Nucleotide Phosphodiesterases
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metabolism Animals Blotting, Western Cell Differentiation / drug effects Cell Survival Cells, Cultured Image Processing, Computer-Assisted Immunohistochemistry Immunologic Factors / pharmacology* Oligodendroglia / drug effects*, metabolism, pathology Rats Simvastatin / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Immunologic Factors; 79902-63-9/Simvastatin; EC 3.1.4.-/2',3'-Cyclic-Nucleotide Phosphodiesterases |
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