title: Hes1, a Notch signaling downstream target, regulates adult hippocampal neurogenesis following traumatic brain injury.
abstract: Hairy and enhancer of split 1 (Hes1), a downstream target of Notch signaling, has long been recognized as crucial in inhibiting neuronal differentiation. However, the role of Hes1 following traumatic brain injury (TBI) in adult neurogenesis in the mouse dentate gyrus (DG) remains partially understood. Here, we investigate the role of Hes1 in regulating neurogenesis in the DG of the adult hippocampus after TBI by up- or downregulating Hes1 expression. First, adenovirus-mediated gene transfection was employed to upregulate Hes1 in vivo. The mice were then subjected to TBI, and the hippocampal tissue was collected for Western blot analysis at designated times, pre- and post-injury. Moreover, the brain slices were stained for BrdU and doublecortin (DCX). We show that enhancing Hes1 inhibits the proliferation and differentiation of neural precursor cells (NPCs) in the DG of the hippocampus soon after TBI. Second, downregulation of Hes1 via RNA interference (RNAi) results in a significant increase in neuronal production and promotes the differentiation of NPCs into mature neurons in the DG, as assessed by BrdU and NeuN double staining. Furthermore, a Morris water maze (MWM) test clearly confirmed that the knockdown of Hes1 improves the spatial learning and memory capacity of adult mice following injury. Taken together, these observations suggest that Hes1 represents a negative regulator of adult neurogenesis post-TBI and that the precise space-time regulation of Hes1 expression in the DG may promote the recovery of neural function following TBI.
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: paperzzhang@gmail.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin 5th Central Hospital, Tianjin 300052, PR China. Electronic address: rongy198628@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, PR China. Electronic address: dake413@163.com.
authors.forename: Qi
authors.initials: Q
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. Electronic address: lijiacdmc@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
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: xiaokuikang@163.com.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Kang
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: Ryyouu@sina.com.
authors.forename: Haining
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Linyi People׳s Hospital, Linyi 276000, PR China. Electronic address: uqqc@163.com.
authors.forename: Linchun
authors.initials: L
authors.lastname: Huan
authors.affiliation: Department of Neurosurgery, Tianjin 5th Central Hospital, Tianjin 300052, PR China. Electronic address: zhang_lin1985@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Heji Hospital affiliated Changzhi Medical College, 271 Taihang East Road, Changzhi 046000, PR China. Electronic address: 76484906@qq.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
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: 18622000583@163.com.
authors.forename: Shuyuan
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: jianningzhang@hotmail.com.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Heji Hospital affiliated Changzhi Medical College, 271 Taihang East Road, Changzhi 046000, PR China. Electronic address: 76484906@qq.com.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ren
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: Xinyu
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001930:Brain Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011897:Random Allocation; D065852:Spatial Memory / Q000502:physiology; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000089662:Doublecortin Protein; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C000714847:Dcx protein, mouse; C489734:Hes1 protein, mouse
keywords: Adult neurogenesis; Dentate gyrus; Hes1; Notch signaling; Traumatic brain injury