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

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...

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Autores principales: Wu, Jingchuan, Li, Hui, He, Junchi, Tian, Xiaocui, Luo, Shuilian, Li, Jiankang, Li, Wei, Zhong, Jianjun, Zhang, Hongrong, Huang, Zhijian, Sun, Xiaochuan, Jiang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790831/
https://www.ncbi.nlm.nih.gov/pubmed/33414448
http://dx.doi.org/10.1038/s41419-020-03329-5
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author Wu, Jingchuan
Li, Hui
He, Junchi
Tian, Xiaocui
Luo, Shuilian
Li, Jiankang
Li, Wei
Zhong, Jianjun
Zhang, Hongrong
Huang, Zhijian
Sun, Xiaochuan
Jiang, Tao
author_facet Wu, Jingchuan
Li, Hui
He, Junchi
Tian, Xiaocui
Luo, Shuilian
Li, Jiankang
Li, Wei
Zhong, Jianjun
Zhang, Hongrong
Huang, Zhijian
Sun, Xiaochuan
Jiang, Tao
author_sort Wu, Jingchuan
collection PubMed
description 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.
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spelling pubmed-77908312021-01-14 (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 Cell Death Dis Article 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. Nature Publishing Group UK 2021-01-05 /pmc/articles/PMC7790831/ /pubmed/33414448 http://dx.doi.org/10.1038/s41419-020-03329-5 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Jingchuan
Li, Hui
He, Junchi
Tian, Xiaocui
Luo, Shuilian
Li, Jiankang
Li, Wei
Zhong, Jianjun
Zhang, Hongrong
Huang, Zhijian
Sun, Xiaochuan
Jiang, Tao
(Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title_full (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title_fullStr (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title_full_unstemmed (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title_short (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
title_sort (downregulation of microrna-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790831/
https://www.ncbi.nlm.nih.gov/pubmed/33414448
http://dx.doi.org/10.1038/s41419-020-03329-5
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