Inhibition of Elevated Hippocampal CD24 Reduces Neurogenesis in Mice With Traumatic Brain Injury

J Surg Res. 2020 Jan:245:321-329. doi: 10.1016/j.jss.2019.07.082. Epub 2019 Aug 14.

Abstract

In the adult rodents' brain, CD24 expression is restricted to immature neurons located in the neurogenesis areas. Our previous studies have confirmed that CD24 expression could be markedly elevated in the cerebral cortex after traumatic brain injury (TBI) both in humans and in mice. Although there is a close relationship between CD24 and neurogenesis, it remains unknown about the specific role of CD24 in neurogenesis areas after TBI. Here, the expression of CD24 was detected in the ipsilateral hippocampus by the Western blotting and real-time quantitative polymerase chain reaction. RNA interference was applied to investigate the effects of CD24 on post-traumatic neurogenesis. Brain sections were labeled with CD24 and doublecortin (DCX) via immunofluorescence. The Morris water maze test was used to assess cognitive functions. The results indicated that both mRNA and protein levels of CD24 were markedly elevated in the hippocampus after TBI. Meanwhile, TBI could cause a decrease of DCX-positive cells in the dentate gyrus of the hippocampus. Downregulation of CD24 significantly inhibited the phosphorylation of Src homology region 2-containing protein tyrosine phosphatase 2 in the ipsilateral hippocampus. Meanwhile, inhibition of CD24 could reduce the number of DCX-positive cells in the dentate gyrus area and impair cognitive functions of the TBI mice. These data suggested that hippocampal expression of CD24 might positively regulate neurogenesis and improve cognitive functions after TBI.

Keywords: CD24; Cognitive function; Neurogenesis; SHP-2; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / physiopathology*
  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism*
  • Cognition / physiology*
  • Disease Models, Animal
  • Doublecortin Protein
  • Down-Regulation
  • Hippocampus / physiopathology*
  • Humans
  • Male
  • Maze Learning
  • Mice
  • Neurogenesis / physiology*
  • Neurons / physiology
  • RNA, Small Interfering / metabolism
  • Recovery of Function
  • Up-Regulation

Substances

  • CD24 Antigen
  • Cd24a protein, mouse
  • Dcx protein, mouse
  • Doublecortin Protein
  • RNA, Small Interfering