title: GSK3β inhibition accelerates axon debris clearance and new axon remyelination.
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 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 β-catenin and provoking its nuclear localization in vivo. 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-related genes. Taken together, our results provide the first evidence that the GSK3β 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 GSK3β inhibitors such as lithium.
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Yixun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's HospitalBeijing, China; Department of Spine Surgery, Peking University Shenzhen HospitalShenzhen, China.
authors.forename: Duanyang
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Mingtai
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Youlai
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Zhongdi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Peixun
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Trauma, Peking University People's Hospital Beijing, China.
authors.forename: Baoguo
authors.initials: B
authors.lastname: Jiang
keywords: GSK3β; LiCl; Peripheral nerve injury; Wnt signals; myelin clearance