Pubmed-entry ::= {
  pmid 20857509,
  medent {
    em std {
      year 2010,
      month 10,
      day 12
    },
    cit {
      title {
        name "Simvastatin interferes with process outgrowth and branching of
 oligodendrocytes."
      },
      authors {
        names ml {
          "Smolders I",
          "Smets I",
          "Maier O",
          "vandeVen M",
          "Steels P",
          "Ameloot M"
        },
        affil str "Biomedical Research Institute, School of Life Sciences,
 Hasselt University and Transnational University Limburg, Diepenbeek, Belgium."
      },
      from journal {
        title {
          iso-jta "J. Neurosci. Res.",
          ml-jta "J Neurosci Res",
          issn "1097-4547",
          name "Journal of neuroscience research"
        },
        imp {
          date std {
            year 2010,
            month 11,
            day 15
          },
          volume "88",
          issue "15",
          pages "3361-3375",
          language "eng",
          pubstatus ppublish,
          history {
            {
              pubstatus other,
              date std {
                year 2010,
                month 9,
                day 22,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus pubmed,
              date std {
                year 2010,
                month 9,
                day 22,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus medline,
              date std {
                year 2011,
                month 1,
                day 28,
                hour 6,
                minute 0
              }
            }
          }
        }
      },
      ids {
        doi "10.1002/jnr.22490",
        pubmed 20857509
      }
    },
    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 muM, 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.",
    mesh {
      {
        term "2',3'-Cyclic-Nucleotide Phosphodiesterases",
        qual {
          {
            subh "metabolism"
          }
        }
      },
      {
        term "Animals"
      },
      {
        term "Blotting, Western"
      },
      {
        term "Cell Differentiation",
        qual {
          {
            subh "drug effects"
          }
        }
      },
      {
        term "Cell Survival"
      },
      {
        term "Cells, Cultured"
      },
      {
        term "Image Processing, Computer-Assisted"
      },
      {
        term "Immunohistochemistry"
      },
      {
        term "Immunologic Factors",
        qual {
          {
            mp TRUE,
            subh "pharmacology"
          }
        }
      },
      {
        term "Oligodendroglia",
        qual {
          {
            mp TRUE,
            subh "drug effects"
          },
          {
            subh "metabolism"
          },
          {
            subh "pathology"
          }
        }
      },
      {
        term "Rats"
      },
      {
        term "Simvastatin",
        qual {
          {
            mp TRUE,
            subh "pharmacology"
          }
        }
      }
    },
    substance {
      {
        type nameonly,
        name "Immunologic Factors"
      },
      {
        type cas,
        cit "79902-63-9",
        name "Simvastatin"
      },
      {
        type ec,
        cit "3.1.4.-",
        name "2',3'-Cyclic-Nucleotide Phosphodiesterases"
      }
    },
    pmid 20857509,
    pub-type {
      "Journal Article",
      "Research Support, Non-U.S. Gov't"
    },
    status medline
  }
}

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