Negative Impact of Statins on Oligodendrocytes and Myelin Formation In Vitro and In Vivo

被引:70
作者
Klopfleisch, Steve [1 ]
Merkler, Doron [2 ]
Schmitz, Matthias [1 ]
Kloeppner, Sabine [1 ]
Schedensack, Mariann [2 ]
Jeserich, Gunnar [5 ]
Althaus, Hans H. [1 ]
Brueck, Wolfgang [2 ,3 ,4 ]
机构
[1] Max Planck Inst Expt Med, D-37075 Gottingen, Germany
[2] Univ Gottingen, Univ Med Ctr, Dept Neuropathol, D-37075 Gottingen, Germany
[3] Inst Multiple Sclerosis Res, Gemeinnutzige Hertie Stiftung, D-37073 Gottingen, Germany
[4] Univ Med Ctr Gottingen, D-37073 Gottingen, Germany
[5] Univ Osnabruck, Dept Neurobiol, D-49076 Osnabruck, Germany
关键词
remyelination; multiple sclerosis; statins; cuprizone; oligodendrocytes; GTPases;
D O I
10.1523/JNEUROSCI.2765-08.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Statins are widely prescribed drugs in cardiovascular diseases. Recent studies also demonstrated anti-inflammatory and immunomodulatory properties of statins by modulating the activity of small GTPases. Statins are thus considered as potential therapeutic drug for the inflammatory demyelinating disease multiple sclerosis ( MS). However, little is known about the effects of statins on myelin-forming oligodendrocytes. Here, we show that statins hamper process and myelin formation in vitro by interfering with Ras and Rho signaling in mature oligodendrocytes and provide evidence that statins impair ongoing remyelination in vivo. Our findings may have significant implications for the application of statins in MS patients and in other demyelinating diseases of the CNS.
引用
收藏
页码:13609 / 13614
页数:6
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