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GSK3ß inhibition accelerates axon debris clearance and new axon remyelination.
Chen, Yixun; Weng, Jian; Han, Duanyang; Chen, Bo; Ma, Mingtai; Yu, Youlai; Li, Ming; Liu, Zhongdi; Zhang, Peixun; Jiang, Baoguo.
Afiliación
  • Chen Y; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Weng J; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Han D; Department of Orthopedics and Trauma, Peking University People's HospitalBeijing, China; Department of Spine Surgery, Peking University Shenzhen HospitalShenzhen, China.
  • Chen B; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Ma M; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Yu Y; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Li M; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Liu Z; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Zhang P; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
  • Jiang B; Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
Am J Transl Res ; 8(12): 5410-5420, 2016.
Article en En | MEDLINE | ID: mdl-28078012
Glycogen synthase kinase 3ß (GSK3ß) inhibitors, especially the mood stabilizer lithium chloride, are also used as neuroprotective or anti-inflammatory agents. We studied the influence of LiCl on inducing early myelin clearance and on regulating the remyelination following peripheral nerves injury. We showed that the oral administration of adult mice with LiCl after sciatic nerve crush injury accelerated in vivo myelin debris clearance stimulated the expression of myelin proteins, restored the myelin structure, and accelerated the recovery of sciatic functions. LiCl treatment also promoted remyelination of the sciatic nerve after crush. Furthermore, we also demonstrated that LiCl exerts its action in Schwann cells by increasing the amount of ß-catenin and provoking its nuclear localization in vivo. We showed by ChIP experiments that LiCl treatment drives ß-catenin to bind to T-cell factor/lymphoid-enhancer factor response elements identified in myelin-related genes. Taken together, our results provide the first evidence that the GSK3ß could be considered as an important drug in inducing early myelin debris clearance and regulating the expression of myelin genes, which open new approaches in the clinical treatment of nerve injuries by utilizing GSK3ß inhibitors such as lithium.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Am J Transl Res Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Am J Transl Res Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos