title: Survivin, a key component of the Wnt/β-catenin signaling pathway, contributes to traumatic brain injury-induced adult neurogenesis in the mouse dentate gyrus.
abstract: The enhancement of endogenous neurogenesis has been suggested in the treatment of traumatic brain injury (TBI); however, the factors that trigger the process of adult neurogenesis following TBI remain elusive. In the adult mammalian central nervous system, there are 2 neurogenic regions: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles, both of which maintain relatively quiescent states in a stable microenvironment. However, once stimulated by intrinsic and extrinsic events, relevant signals are activated in these 2 regions. In this study, in order to explore the mechanisms behind endogenous neurogenesis following TBI, we investigated potential factors regulating this process. We observed that the expression of survivin, an anti-apoptotic protein, increased in a time-dependent manner in the hippocampus in a mouse model of TBI. In addition, the number of survivin (+) cells, as well as that of BrdU (+) cells increased in the SGZ of the dentate gyrus (DG) in the hippocampus following TBI, as shown by immunofluorescence double staining; the co-localization of survivin and BrdU was shown in the merged images. The expression of survivin was also significantly increased in the doublecortin (DCX) (+) immature neurons in the DG of the hippocampus soon after the induction of TBI. Taken together, these data confirm the connection between the expression of survivin and adult neurogenesis following TBI; our data also suggest the therapeutic potential of upregulating survivin expression as a novel strategy for the effective treatment of TBI.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Haining
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Kang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yang
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000166:cytology / Q000473:pathology; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: C117749:Birc5 protein, mouse; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin