title: Lithium enhances remyelination of peripheral nerves.
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.
authors.affiliation: Unité Mixte de Recherche 8194, Centre National de la Recherche Scientifique, University Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Makoukji
authors.forename: Martin
authors.initials: M
authors.lastname: Belle
authors.forename: Delphine
authors.initials: D
authors.lastname: Meffre
authors.forename: Ruth
authors.initials: R
authors.lastname: Stassart
authors.forename: Julien
authors.initials: J
authors.lastname: Grenier
authors.forename: Ghjuvan'Ghjacumu
authors.initials: G
authors.lastname: Shackleford
authors.forename: Robert
authors.initials: R
authors.lastname: Fledrich
authors.forename: Cosima
authors.initials: C
authors.lastname: Fonte
authors.forename: Julien
authors.initials: J
authors.lastname: Branchu
authors.forename: Marie
authors.initials: M
authors.lastname: Goulard
authors.forename: Catherine
authors.initials: C
authors.lastname: de Waele
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charbonnier
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sereda
authors.forename: Etienne-Emile
authors.initials: EE
authors.lastname: Baulieu
authors.forename: Michael
authors.initials: M
authors.lastname: Schumacher
authors.forename: Sophie
authors.initials: S
authors.lastname: Bernard
authors.forename: Charbel
authors.initials: C
authors.lastname: Massaad
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018993:Myelin P0 Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry*; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism*; D010919:Placebos; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D015398:Signal Transduction
chemical_list: C560546:Mpz protein, mouse; D018993:Myelin P0 Protein; D010919:Placebos; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride