PMID- 33414448
OWN - NLM
STAT- MEDLINE
DCOM- 20211001
LR  - 20230127
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 1
DP  - 2021 Jan 5
TI  - (Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic 
      phase after traumatic brain injury).
PG  - 9
LID - 10.1038/s41419-020-03329-5 [doi]
LID - 9
AB  - 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-beta-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.
FAU - Wu, Jingchuan
AU  - Wu J
AUID- ORCID: 0000-0002-1213-4888
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
AD  - Department of Neurosurgery, General Hospital of The YangTze River Shipping, Wuhan 
      Brain Hospital, Wuhan, Hubei, 430014, China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - He, Junchi
AU  - He J
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Tian, Xiaocui
AU  - Tian X
AD  - College of Pharmacy, Chongqing Key Laboratory of Biochemistry and Molecular 
      Pharmacology, Chongqing Medical University, Chongqing, Yuzhong, 400016, China.
FAU - Luo, Shuilian
AU  - Luo S
AD  - Department of Ultrasound, Zhongnan Hospital of WuHan University, Wuhan, 430071, 
      China.
FAU - Li, Jiankang
AU  - Li J
AD  - Dept of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon, 
      Hong Kong, China.
FAU - Li, Wei
AU  - Li W
AD  - BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 
      518083, China.
FAU - Zhong, Jianjun
AU  - Zhong J
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Zhang, Hongrong
AU  - Zhang H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Huang, Zhijian
AU  - Huang Z
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Sun, Xiaochuan
AU  - Sun X
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China. sunxch1445@qq.com.
FAU - Jiang, Tao
AU  - Jiang T
AUID- ORCID: 0000-0002-8529-4487
AD  - Department of Neurosurgery, Beijing TianTan Hospital, Capital Medical University, 
      Beijing, 100050, China. zacharytaojiang@163.com.
AD  - Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, 
      China. zacharytaojiang@163.com.
AD  - China National Clinical Research Center for Neurological diseases, Beijing, 
      China. zacharytaojiang@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210105
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (MIRN9 microRNA, rat)
RN  - 0 (MicroRNAs)
SB  - IM
EIN - Cell Death Dis. 2021 Mar 3;12(3):233. PMID: 33658477
MH  - Animals
MH  - Brain Injuries, Traumatic/*genetics
MH  - Down-Regulation
MH  - MicroRNAs/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synapses/*metabolism
PMC - PMC7790831
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/01/09 06:00
MHDA- 2021/10/02 06:00
PMCR- 2021/01/05
CRDT- 2021/01/08 06:05
PHST- 2020/05/26 00:00 [received]
PHST- 2020/12/07 00:00 [accepted]
PHST- 2020/12/03 00:00 [revised]
PHST- 2021/01/08 06:05 [entrez]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/10/02 06:00 [medline]
PHST- 2021/01/05 00:00 [pmc-release]
AID - 10.1038/s41419-020-03329-5 [pii]
AID - 3329 [pii]
AID - 10.1038/s41419-020-03329-5 [doi]
PST - epublish
SO  - Cell Death Dis. 2021 Jan 5;12(1):9. doi: 10.1038/s41419-020-03329-5.