Proceedings of the National Academy of Sciences - PNAS, 2012-03, Vol.109 (10), p.3973-3978
2012
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- Autor(en) / Beteiligte
- Titel
- Lithium enhances remyelination of peripheral nerves
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-03, Vol.109 (10), p.3973-3978
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1121367109Titel-ID: cdi_jstor_primary_41507069
- Format
- –
- Schlagworte
- Animals, anti-inflammatory agents, Antiinflammatory agents, Axons, Biological Sciences, catenin, Cell lines, Cell Nucleus - metabolism, Demyelination, Facial nerve, Gene expression, Genes, glycogen, Glycogen synthase kinase 3, Glycogen Synthase Kinase 3 - metabolism, Glycogen Synthase Kinase 3 beta, Injuries, Kinases, Lithium, Lithium chloride, Lithium Chloride - pharmacology, Male, Mice, Mice, Inbred C57BL, Mood, Myelin, Myelin P0 Protein - metabolism, myelin sheath, Myelin Sheath - chemistry, Myelination, nerve tissue, Nerves, Neuroprotection, Peripheral myelin protein 22, Peripheral nerves, Peripheral Nerves - drug effects, Peripheral Nerves - metabolism, Physical trauma, Placebos, Promoters, Proto-Oncogene Proteins c-akt - metabolism, Regulatory sequences, response elements, Rodents, Schwann cells, Schwann Cells - metabolism, Sciatic nerve, Sciatic Nerve - injuries, Signal Transduction, Transcription factors