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Hes1, a Notch signaling downstream target, regulates adult hippocampal neurogenesis following traumatic brain injury

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 understoo... Full description

Journal Title: Brain Research 02 October 2014, Vol.1583, pp.65-78
Main Author: Zhang, Zhen
Other Authors: Yan, Rong , Zhang, Qi , Li, Jia , Kang, Xiaokui , Wang, Haining , Huan, Linchun , Zhang, Lin , Li, Fan , Yang, Shuyuan , Zhang, Jianning , Ren, Xinliang , Yang, Xinyu
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0006-8993 ; E-ISSN: 1872-6240 ; DOI: 10.1016/j.brainres.2014.07.037
Link: https://www.sciencedirect.com/science/article/pii/S0006899314009883
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recordid: elsevier_sdoi_10_1016_j_brainres_2014_07_037
title: Hes1, a Notch signaling downstream target, regulates adult hippocampal neurogenesis following traumatic brain injury
format: Article
creator:
  • Zhang, Zhen
  • Yan, Rong
  • Zhang, Qi
  • Li, Jia
  • Kang, Xiaokui
  • Wang, Haining
  • Huan, Linchun
  • Zhang, Lin
  • Li, Fan
  • Yang, Shuyuan
  • Zhang, Jianning
  • Ren, Xinliang
  • Yang, Xinyu
subjects:
  • Hes1
  • Notch Signaling
  • Adult Neurogenesis
  • Dentate Gyrus
  • Traumatic Brain Injury
  • Anatomy & Physiology
ispartof: Brain Research, 02 October 2014, Vol.1583, pp.65-78
description: 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 in regulating neurogenesis in the DG of the adult hippocampus after TBI by up- or downregulating expression. First, adenovirus-mediated gene transfection was employed to upregulate 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 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 improves the spatial learning and memory capacity of adult mice following injury. Taken together, these observations suggest that 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.
language: eng
source:
identifier: ISSN: 0006-8993 ; E-ISSN: 1872-6240 ; DOI: 10.1016/j.brainres.2014.07.037
fulltext: fulltext
issn:
  • 0006-8993
  • 00068993
  • 1872-6240
  • 18726240
url: Link


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titleHes1, a Notch signaling downstream target, regulates adult hippocampal neurogenesis following traumatic brain injury
creatorZhang, Zhen ; Yan, Rong ; Zhang, Qi ; Li, Jia ; Kang, Xiaokui ; Wang, Haining ; Huan, Linchun ; Zhang, Lin ; Li, Fan ; Yang, Shuyuan ; Zhang, Jianning ; Ren, Xinliang ; Yang, Xinyu
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subjectHes1 ; Notch Signaling ; Adult Neurogenesis ; Dentate Gyrus ; Traumatic Brain Injury ; Anatomy & Physiology
descriptionHairy 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 in regulating neurogenesis in the DG of the adult hippocampus after TBI by up- or downregulating expression. First, adenovirus-mediated gene transfection was employed to upregulate 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 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 improves the spatial learning and memory capacity of adult mice following injury. Taken together, these observations suggest that 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.
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