PMID- 30522932
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20231006
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 39
DP  - 2019 Jan
TI  - A novel mechanism of synaptic and cognitive impairments mediated via microRNA-30b 
      in Alzheimer's disease.
PG  - 409-421
LID - S2352-3964(18)30563-2 [pii]
LID - 10.1016/j.ebiom.2018.11.059 [doi]
AB  - BACKGROUND: It is widely accepted that cognitive and memory deficits in 
      Alzheimer's disease (AD) primarily result from synaptic failure. However, the 
      mechanisms that underlie synaptic and cognitive dysfunction remain unclear. 
      METHODS: We utilized molecular biology techniques, electrophysiological 
      recordings, fluorescence in situ hybridization (FISH), immuno- and 
      Golgi-staining, chromatin immunoprecipitation (CHIP); lentivirus (LV)-based 
      microRNA overexpression and 'sponging', and behavioral tests to assess 
      upregulated miR-30b causing synaptic and cognitive declines in APP transgenic 
      (TG) mice. FINDINGS: We provide evidence that expression of miR-30b, which 
      targets molecules important for maintaining synaptic integrity, including ephrin 
      type-B receptor 2 (ephB2), sirtuin1 (sirt1), and glutamate ionotropic receptor 
      AMPA type subunit 2 (GluA2), is robustly upregulated in the brains of both AD 
      patients and APP transgenic (TG) mice, an animal model of AD, while expression of 
      its targets is significantly downregulated. Overexpression of miR-30b in the 
      hippocampus of normal wild-type (WT) mice impairs synaptic and cognitive 
      functions, mimicking those seen in TG mice. Conversely, knockdown of endogenous 
      miR-30b in TG mice prevents synaptic and cognitive decline. We further observed 
      that expression of miR-30b is upregulated by proinflammatory cytokines and Abeta42 
      through NF-kappaB signaling. INTERPRETATION: Our results provide a previously 
      undefined mechanism by which unregulated miR-30b causes synaptic and cognitive 
      dysfunction in AD, suggesting that reversal of dysregulated miR-30b in the brain 
      may prevent or slow cognitive declines in AD. FUND: This work was supported by 
      National Institutes of Health grants R01NS076815, R01MH113535, R01AG058621, 
      P30GM103340 Pilot Project, and by the LSUHSC School of Medicine Research 
      Enhancement Program grant (to C.C.).
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Song, Yunping
AU  - Song Y
AD  - Neuroscience Center of Excellence, Louisiana State University Health Sciences 
      Center, New Orleans, LA 70112, USA.
FAU - Hu, Mei
AU  - Hu M
AD  - Neuroscience Center of Excellence, Louisiana State University Health Sciences 
      Center, New Orleans, LA 70112, USA.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Neuroscience Center of Excellence, Louisiana State University Health Sciences 
      Center, New Orleans, LA 70112, USA.
FAU - Teng, Zhao-Qian
AU  - Teng ZQ
AD  - Neuroscience Center of Excellence, Louisiana State University Health Sciences 
      Center, New Orleans, LA 70112, USA.
FAU - Chen, Chu
AU  - Chen C
AD  - Neuroscience Center of Excellence, Louisiana State University Health Sciences 
      Center, New Orleans, LA 70112, USA; Department of Otorhinolaryngology, Louisiana 
      State University Health Sciences Center, New Orleans, LA 70112, USA. Electronic 
      address: cchen@lsuhsc.edu.
LA  - eng
GR  - P30 GM103340/GM/NIGMS NIH HHS/United States
GR  - R01 AG058621/AG/NIA NIH HHS/United States
GR  - R01 MH113535/MH/NIMH NIH HHS/United States
GR  - R01 NS076815/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20181203
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (MIRN30b microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Alzheimer Disease/*genetics/psychology
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Animals
MH  - Cells, Cultured
MH  - Cognitive Dysfunction/*genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Male
MH  - Maze Learning
MH  - Mice
MH  - Mice, Transgenic
MH  - MicroRNAs/*genetics
MH  - Signal Transduction
MH  - Synaptic Potentials
PMC - PMC6354659
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Dementia
OT  - Neuroinflammation
OT  - Nuclear factor kappa B
OT  - Small noncoding RNA
OT  - Synaptic failure
OT  - miRNA sponge
EDAT- 2018/12/14 06:00
MHDA- 2019/06/14 06:00
PMCR- 2018/12/03
CRDT- 2018/12/08 06:00
PHST- 2018/10/12 00:00 [received]
PHST- 2018/11/20 00:00 [revised]
PHST- 2018/11/27 00:00 [accepted]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/12/08 06:00 [entrez]
PHST- 2018/12/03 00:00 [pmc-release]
AID - S2352-3964(18)30563-2 [pii]
AID - 10.1016/j.ebiom.2018.11.059 [doi]
PST - ppublish
SO  - EBioMedicine. 2019 Jan;39:409-421. doi: 10.1016/j.ebiom.2018.11.059. Epub 2018 
      Dec 3.