title: Inhibition of gecko GSK-3β promotes elongation of neurites and oligodendrocyte processes but decreases the proliferation of blastemal cells.
abstract: GSK-3β signaling is involved in regulation of both neuronal and glial cell functions, and interference of the signaling affects central nervous system (CNS) development and regeneration. Thus, GSK-3β was proposed to be an important therapeutic target for promoting functional recovery of adult CNS injuries. To further clarify the regulatory function of the kinase on the CNS regeneration, we characterized gecko GSK-3β and determined the effects of GSK-3β inactivation on the neuronal and glial cell lines, as well as on the gecko tail (including spinal cord) regeneration. Gecko GSK-3β shares 91.7-96.7% identity with those of other vertebrates, and presented higher expression abundance in brain and spinal cord. The kinase strongly colocalized with the oligodendrocytes while less colocalized with neurons in the spinal cord. Phosphorylated GSK-3β (pGSK-3β) levels decreased gradually during the normally regenerating spinal cord ranging from L13 to the 6th caudal vertebra. Lithium injection increased the pGSK-3β levels of the corresponding spinal cord segments, and in vitro experiments on neurons and oligodendrocyte cell line revealed that the elevation of pGSK-3β promoted elongation of neurites and oligodendrocyte processes. In the normally regenerate tails, pGSK-3β kept stable in 2 weeks, whereas decreased at 4 weeks. Injection of lithium led to the elevation of pGSK-3β levels time-dependently, however destructed the regeneration of the tail including spinal cord. Bromodeoxyuridine (BrdU) staining demonstrated that inactivation of GSK-3β decreased the proliferation of blastemal cells. Our results suggested that species-specific regulation of GSK-3β was indispensable for the complete regeneration of CNS.
authors.affiliation: Key Laboratory of Neuroregeneration, Nantong University, Nantong 226007, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Dong
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhou
authors.forename: Honghua
authors.initials: H
authors.lastname: Song
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Gu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008094:Lithium / Q000494:pharmacology; D008116:Lizards; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure*; D009457:Neuroglia / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function; D016415:Sequence Alignment; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D058630:Spinal Cord Regeneration; D013623:Tail / Q000601:surgery
chemical_list: D012333:RNA, Messenger; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3