PMID- 35041806
OWN - NLM
STAT- MEDLINE
DCOM- 20220330
LR  - 20220330
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 207
DP  - 2022 Apr 1
TI  - Upregulation of miR-19b-3p exacerbates chronic stress-induced changes in synaptic 
      plasticity and cognition by targeting Drebrin.
PG  - 108951
LID - S0028-3908(22)00010-7 [pii]
LID - 10.1016/j.neuropharm.2022.108951 [doi]
AB  - Chronic stress is associated with impairment of synapse plasticity in hippocampus 
      and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is 
      believed to take responsibility for dendritic atrophy and reduction of spine 
      number induced by chronic stress in hippocampus. But little is known about the 
      molecular mechanisms underlying CORT induced abnormal synapse plasticity and 
      cognitive dysfunction. Drebrin is an F-actin binding protein that modulates 
      memory formation and maintenance by controlling the genesis and morphology of 
      dendritic spines. In addition, miRNAs have been reported to participate in the 
      negative regulation of protein-coding genes. In this study, five miRNAs capable 
      of targeting Drebrin were selected by searching miRNA databases. One of these 
      miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of 
      mice with chronic restraint stress (CRS). Luciferase reporter assay and 
      Fluorescence in situ hybridization (FISH) were employed to identify the 
      interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p 
      expression in vivo using an antagomir or in vitro using an inhibitor increased 
      Drebrin expression, ameliorated the abnormal dendritic structure and upregulated 
      the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary 
      hippocampal neurons cultured under CORT stimulation, respectively. 
      Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the 
      limited synaptic transmission and synaptic plasticity in hippocampal neurons. 
      Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in 
      CRS mice. These in vivo and in vitro findings indicate that the upregulation of 
      miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive 
      impairment by targeting Drebrin.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Chen, Jingli
AU  - Chen J
AD  - Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      Hubei, China; Department of Anesthesiology, The Central Hospital of Wuhan, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, 430014, 
      Hubei, China.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, 
      China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central 
      Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, 430014, Hubei, China.
FAU - Xu, Mu
AU  - Xu M
AD  - Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, 
      China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central 
      Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, 430014, Hubei, China.
FAU - Zhu, Jiaxi
AU  - Zhu J
AD  - Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, 
      China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central 
      Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, 430014, Hubei, China.
FAU - Xia, Zhongyuan
AU  - Xia Z
AD  - Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      Hubei, China. Electronic address: xiazhongyuan2005@aliyun.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220115
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antagomirs)
RN  - 0 (MIRN19 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Neuropeptides)
RN  - 0 (drebrins)
SB  - IM
MH  - Animals
MH  - Antagomirs
MH  - CA1 Region, Hippocampal
MH  - Cells, Cultured
MH  - Cognitive Dysfunction/etiology/*metabolism
MH  - Mice
MH  - MicroRNAs/drug effects/*metabolism
MH  - Neuronal Plasticity/*physiology
MH  - Neuropeptides/*metabolism
MH  - Pyramidal Cells
MH  - Stress, Psychological/complications
MH  - Up-Regulation
OTO - NOTNLM
OT  - Anxiety
OT  - Chronic stress
OT  - Cognitive dysfunction
OT  - Cytoskeleton
OT  - Drebrin
OT  - Hippocampal neurons
OT  - MicroRNA
OT  - Synaptic plasticity
EDAT- 2022/01/19 06:00
MHDA- 2022/03/31 06:00
CRDT- 2022/01/18 20:11
PHST- 2021/09/08 00:00 [received]
PHST- 2021/12/09 00:00 [revised]
PHST- 2022/01/12 00:00 [accepted]
PHST- 2022/01/19 06:00 [pubmed]
PHST- 2022/03/31 06:00 [medline]
PHST- 2022/01/18 20:11 [entrez]
AID - S0028-3908(22)00010-7 [pii]
AID - 10.1016/j.neuropharm.2022.108951 [doi]
PST - ppublish
SO  - Neuropharmacology. 2022 Apr 1;207:108951. doi: 10.1016/j.neuropharm.2022.108951. 
      Epub 2022 Jan 15.