Lithium enhances remyelination of peripheral nerves
| Autor: | Ruth M. Stassart, Michael Schumacher, Delphine Meffre, Etienne-Emile Baulieu, Robert Fledrich, Sophie Bernard, Martin Belle, Ghjuvan’ Ghjacumu Shackleford, Julien Branchu, Joelle Makoukji, Marie Goulard, Catherine de Waele, Frédéric Charbonnier, Julien Grenier, Cosima Fonte, Charbel Massaad, Michael W. Sereda |
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| Rok vydání: | 2012 |
| Předmět: |
Male
inorganic chemicals Biology Neuroprotection Placebos Glycogen Synthase Kinase 3 Mice Myelin chemistry.chemical_compound GSK-3 medicine Animals Peripheral Nerves Remyelination GSK3B Myelin Sheath Cell Nucleus Glycogen Synthase Kinase 3 beta Multidisciplinary Biological Sciences medicine.disease Sciatic Nerve Cell biology Mice Inbred C57BL medicine.anatomical_structure nervous system chemistry Crush injury Lithium chloride Schwann Cells Sciatic nerve Lithium Chloride Myelin P0 Protein Proto-Oncogene Proteins c-akt Neuroscience Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:3973-3978 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1121367109 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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