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Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3973-8. doi: 10.1073/pnas.1121367109. Epub 2012 Feb 21.

Lithium enhances remyelination of peripheral nerves.

Author information

1
Unité Mixte de Recherche 8194, Centre National de la Recherche Scientifique, University Paris Descartes, 75270 Paris Cedex 06, France.

Abstract

Glycogen synthase kinase 3β (GSK3β) inhibitors, especially the mood stabilizer lithium chloride, are also used as neuroprotective or anti-inflammatory agents. We studied the influence of LiCl on the remyelination of peripheral nerves. We showed that the treatment of adult mice with LiCl after facial nerve crush injury stimulated the expression of myelin genes, restored the myelin structure, and accelerated the recovery of whisker movements. LiCl treatment also promoted remyelination of the sciatic nerve after crush. We also demonstrated that peripheral myelin gene MPZ and PMP22 promoter activities, transcripts, and protein levels are stimulated by GSK3β inhibitors (LiCl and SB216763) in Schwann cells as well as in sciatic and facial nerves. LiCl exerts its action in Schwann cells by increasing the amount of β-catenin and provoking its nuclear localization. We showed by ChIP experiments that LiCl treatment drives β-catenin to bind to T-cell factor/lymphoid-enhancer factor response elements identified in myelin genes. Taken together, our findings open perspectives in the treatment of nerve demyelination by administering GSK3β inhibitors such as lithium.

PMID:
22355115
PMCID:
PMC3309729
DOI:
10.1073/pnas.1121367109
[Indexed for MEDLINE]
Free PMC Article

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