title: Downregulation of survivin regulates adult hippocampal neurogenesis and apoptosis, and inhibits spatial learning and memory following traumatic brain injury.
abstract: Survivin, a unique member of the inhibitor of the apoptosis protein (IAP) family, has been suggested to play a crucial role in promoting the cell cycle and mediates mitosis during embryonic development. However, the role of survivin following traumatic brain injury (TBI) in adult neurogenesis and apoptosis in the mouse dentate gyrus (DG) remains only partially understood. We adopted adenovirus-mediated RNA interference (RNAi) as a means of suppressing the expression of survivin and observed its effects on adult regeneration and neurological function in mice after brain injury. The mice were subjected to TBI, and the ipsilateral hippocampus was then examined using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting analyses. Brain slices were stained for 5'-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX). Our data showed that survivin knockdown inhibits the proliferation and differentiation of neural precursor cells (NPCs) in the DG of the hippocampus soon after TBI. Furthermore, downregulation of survivin results in a significant increase in programmed cell death in the DG, as assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) double staining. The Morris water maze (MWM) test was adopted to evaluate neurological function, which confirmed that knockdown of survivin worsened the memory capacity that was already compromised following TBI. Survivin in adult mice brains after TBI can be successfully down-regulated by RNAi, which inhibited adult hippocampal neurogenesis, promoted apoptotic cell death, and resulted in a negative role in the recovery of dysfunction following injury.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China. Electronic address: yangxinyu@tijmu.edu.cn.
authors.forename: X
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D034622:RNA Interference; D020127:Recovery of Function / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D012097:Repressor Proteins; D000077022:Survivin
keywords: RNAi; adult neurogenesis; dentate gyrus; survivin; traumatic brain injury