PMID- 31924235
OWN - NLM
STAT- MEDLINE
DCOM- 20210212
LR  - 20210212
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 13
IP  - 1
DP  - 2020 Jan 10
TI  - A microRNA signature of toxic extrasynaptic N-methyl-D-aspartate (NMDA) receptor 
      signaling.
PG  - 3
LID - 10.1186/s13041-020-0546-0 [doi]
LID - 3
AB  - The cellular consequences of N-Methyl-D-Aspartate receptor (NMDAR) stimulation 
      depend on the receptors' subcellular localization. Synaptic NMDARs promote 
      plasticity and survival whereas extrasynaptic NMDARs mediate excitotoxicity and 
      contribute to cell death in neurodegenerative diseases. The mechanisms that 
      couple activation of extrasynaptic NMDARs to cell death remain incompletely 
      understood. We here show that activation of extrasynaptic NMDARs by bath 
      application of NMDA or L-glutamate leads to the upregulation of a group of 19 
      microRNAs in cultured mouse hippocampal neurons. In contrast, none of these 
      microRNAs is induced upon stimulation of synaptic activity. Increased microRNA 
      expression depends on the pri-miRNA processing enzyme Drosha, but not on de novo 
      gene transcription. These findings suggest that toxic NMDAR signaling involves 
      changes in the expression levels of particular microRNAs.
FAU - Bas-Orth, Carlos
AU  - Bas-Orth C
AUID- ORCID: 0000-0002-6037-8350
AD  - Department of Neurobiology, Interdisciplinary Center for Neurosciences, 
      Heidelberg University, 69120, Heidelberg, Germany. 
      bas-orth@ana.uni-heidelberg.de.
AD  - Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, 
      Heidelberg University, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany. 
      bas-orth@ana.uni-heidelberg.de.
FAU - Koch, Mirja
AU  - Koch M
AD  - Department of Neurobiology, Interdisciplinary Center for Neurosciences, 
      Heidelberg University, 69120, Heidelberg, Germany.
FAU - Lau, David
AU  - Lau D
AD  - Department of Neurobiology, Interdisciplinary Center for Neurosciences, 
      Heidelberg University, 69120, Heidelberg, Germany.
FAU - Buchthal, Bettina
AU  - Buchthal B
AD  - Department of Neurobiology, Interdisciplinary Center for Neurosciences, 
      Heidelberg University, 69120, Heidelberg, Germany.
FAU - Bading, Hilmar
AU  - Bading H
AD  - Department of Neurobiology, Interdisciplinary Center for Neurosciences, 
      Heidelberg University, 69120, Heidelberg, Germany.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200110
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (MicroRNAs)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 3.1.26.3 (Drosha protein, mouse)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - SIV03811UC (Kainic Acid)
RN  - TE7660XO1C (Glycine)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Animals
MH  - Bicuculline/pharmacology
MH  - Cells, Cultured
MH  - GABA-A Receptor Antagonists/pharmacology
MH  - Glutamic Acid/pharmacology
MH  - Glycine/pharmacology/toxicity
MH  - Hippocampus/cytology
MH  - Kainic Acid/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/biosynthesis/*genetics
MH  - N-Methylaspartate/pharmacology/*toxicity
MH  - Neurotoxins/pharmacology/*toxicity
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Ribonuclease III/physiology
MH  - Seizures/chemically induced
MH  - Signal Transduction/*genetics
MH  - Specific Pathogen-Free Organisms
MH  - Subcellular Fractions/metabolism
MH  - *Transcriptome
MH  - Up-Regulation/drug effects
PMC - PMC6954508
OTO - NOTNLM
OT  - Biomarkers
OT  - Cell death
OT  - Kainate
OT  - MicroRNA
OT  - NMDA receptor
OT  - Neurodegeneration
OT  - Neurotransmitter receptors
OT  - Seizures
COIS- The authors declare that they have no competing interests.
EDAT- 2020/01/12 06:00
MHDA- 2021/02/13 06:00
PMCR- 2020/01/10
CRDT- 2020/01/12 06:00
PHST- 2019/10/15 00:00 [received]
PHST- 2020/01/05 00:00 [accepted]
PHST- 2020/01/12 06:00 [entrez]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2021/02/13 06:00 [medline]
PHST- 2020/01/10 00:00 [pmc-release]
AID - 10.1186/s13041-020-0546-0 [pii]
AID - 546 [pii]
AID - 10.1186/s13041-020-0546-0 [doi]
PST - epublish
SO  - Mol Brain. 2020 Jan 10;13(1):3. doi: 10.1186/s13041-020-0546-0.