Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Jingchuan Wu
  • Hui Li
  • Junchi He
  • Xiaocui Tian
  • Shuilian Luo
  • Wei Li
  • Jianjun Zhong
  • Hongrong Zhang
  • Zhijian Huang
  • Xiaochuan Sun
  • Tao Jiang

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Detail(s)

Original languageEnglish
Article number9
Journal / PublicationCell Death and Disease
Volume12
Online published5 Jan 2021
Publication statusPublished - 2021

Link(s)

Abstract

The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague–Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague–Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-β-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.

Research Area(s)

Citation Format(s)

Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury. / Wu, Jingchuan; Li, Hui; He, Junchi; Tian, Xiaocui; Luo, Shuilian; Li, Jiankang; Li, Wei; Zhong, Jianjun; Zhang, Hongrong; Huang, Zhijian; Sun, Xiaochuan; Jiang, Tao.

In: Cell Death and Disease, Vol. 12, 9, 2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review