Makoukji J et al. Lithium enhances remyelination Proc Natl Acad Sci U S A. 2012 Feb 21. [Epub ahead of print]
Glycogen synthase kinase 3β (GSK3β) inhibitors, especially the mood stabilizer lithium chloride (LiCl). 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 activities, transcripts, and protein levels are stimulated by GSK3β inhibitors (LiCl and SB216763) in Schwann cells (the oligodendrocytes of the peripheral nerve that make myelin) 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.
It remains to be shown whether Lithium has any reparative effect on central nervous system myelin but there is experimental evidence that GSK3beta also controls oligodendrocyte function furthermore lithium may have some immunomodulatory capacity
Treatment was started (arrow up) and stopped (arrow down). Clinical disease ranges from limp tail (score 1) to being paralysed (score 3)
Labels: Lithium, remyelination