PMID- 28488209
OWN - NLM
STAT- MEDLINE
DCOM- 20190204
LR  - 20190215
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 55
IP  - 4
DP  - 2018 Apr
TI  - miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala.
PG  - 3301-3315
LID - 10.1007/s12035-017-0564-9 [doi]
AB  - MicroRNAs are a class of non-coding RNAs with a growing relevance in the 
      regulation of gene expression related to brain function and plasticity. They have 
      the potential to orchestrate complex phenomena, such as the neuronal response to 
      homeostatic challenges. We previously demonstrated the involvement of miR-135a in 
      the regulation of early stress response. In the present study, we examine the 
      role of miR-135a in stress-related behavior. We show that the knockdown (KD) of 
      miR-135a in the mouse amygdala induces an increase in anxiety-like behavior. 
      Consistently with behavioral studies, electrophysiological experiments in acute 
      brain slices indicate an increase of amygdala spontaneous excitatory postsynaptic 
      currents, as a result of miR-135a KD. Furthermore, we presented direct evidences, 
      by in vitro assays and in vivo miRNA overexpression in the amygdala, that two key 
      regulators of synaptic vesicle fusion, complexin-1 and complexin-2, are direct 
      targets of miR-135a. In vitro analysis of miniature excitatory postsynaptic 
      currents on miR-135a KD primary neurons indicates unpaired quantal excitatory 
      neurotransmission. Finally, increased levels of complexin-1 and complexin-2 
      proteins were detected in the mouse amygdala after acute stress, accordingly to 
      the previously observed stress-induced miR-135a downregulation. Overall, our 
      results unravel a previously unknown miRNA-dependent mechanism in the amygdala 
      for regulating anxiety-like behavior, providing evidences of a physiological role 
      of miR-135a in the modulation of presynaptic mechanisms of glutamatergic 
      neurotransmission.
FAU - Mannironi, Cecilia
AU  - Mannironi C
AUID- ORCID: 0000-0001-6934-8425
AD  - Istituto di Biologia e Patologia Molecolari, CNR, c/o Sapienza Universita' di 
      Roma, Rome, Italy. cecilia.mannironi@uniroma1.it.
FAU - Biundo, Antonio
AU  - Biundo A
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
FAU - Rajendran, Samyutha
AU  - Rajendran S
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
AD  - Istituto di Biologia Cellulare e Neurobiologia, CNR, Rome, Italy.
AD  - Centro di Ricerca in Neurobiologia "D. Bovet", Sapienza Universita' di Roma, 
      Rome, Italy.
FAU - De Vito, Francesca
AU  - De Vito F
AD  - Fondazione Santa Lucia, I.R.C.C.S, Rome, Italy.
FAU - Saba, Luana
AU  - Saba L
AD  - Fondazione Santa Lucia, I.R.C.C.S, Rome, Italy.
FAU - Caioli, Silvia
AU  - Caioli S
AD  - Fondazione Santa Lucia, I.R.C.C.S, Rome, Italy.
FAU - Zona, Cristina
AU  - Zona C
AD  - Fondazione Santa Lucia, I.R.C.C.S, Rome, Italy.
AD  - Dipartimento di Medicina dei Sistemi, Universita' di Roma "Tor Vergata", Rome, 
      Italy.
FAU - Ciotti, Teresa
AU  - Ciotti T
AD  - Istituto di Biologia Cellulare e Neurobiologia, CNR, Rome, Italy.
FAU - Caristi, Silvana
AU  - Caristi S
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
FAU - Perlas, Emerald
AU  - Perlas E
AD  - Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo 
      Scalo, Rome, Italy.
FAU - Del Vecchio, Giorgia
AU  - Del Vecchio G
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
FAU - Bozzoni, Irene
AU  - Bozzoni I
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
FAU - Rinaldi, Arianna
AU  - Rinaldi A
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
AD  - Istituto di Biologia Cellulare e Neurobiologia, CNR, Rome, Italy.
AD  - Centro di Ricerca in Neurobiologia "D. Bovet", Sapienza Universita' di Roma, 
      Rome, Italy.
FAU - Mele, Andrea
AU  - Mele A
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
AD  - Istituto di Biologia Cellulare e Neurobiologia, CNR, Rome, Italy.
AD  - Centro di Ricerca in Neurobiologia "D. Bovet", Sapienza Universita' di Roma, 
      Rome, Italy.
FAU - Presutti, Carlo
AU  - Presutti C
AD  - Istituto di Biologia e Patologia Molecolari, CNR, c/o Sapienza Universita' di 
      Roma, Rome, Italy.
AD  - Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Universita' 
      di Roma, Rome, Italy.
LA  - eng
GR  - Project F57I12000110009/Filas/
GR  - AdG 340172-MUNCODD/ERC-2013/
GR  - full grant 2014 "RNA circuitries in Amyotrophic Lateral Sclerosis 
      pathogenesis"/Arisla/
PT  - Journal Article
DEP - 20170509
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn135 microRNA, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (complexin I)
RN  - 0 (complexin II)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics/metabolism
MH  - Amygdala/*metabolism/pathology/*physiopathology
MH  - Animals
MH  - Anxiety/*genetics/*physiopathology
MH  - *Behavior, Animal
MH  - Cell Line, Tumor
MH  - Excitatory Postsynaptic Potentials
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Hippocampus/pathology
MH  - Humans
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurons/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Stress, Physiological/genetics
MH  - Synaptic Transmission/*genetics
OTO - NOTNLM
OT  - Amygdala
OT  - Post-transcriptional regulation
OT  - Stress-related disease
OT  - Synaptic activity
OT  - Synaptic transmission
OT  - miR-135a
OT  - microRNAs
EDAT- 2017/05/11 06:00
MHDA- 2019/02/05 06:00
CRDT- 2017/05/11 06:00
PHST- 2017/02/01 00:00 [received]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2019/02/05 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
AID - 10.1007/s12035-017-0564-9 [pii]
AID - 10.1007/s12035-017-0564-9 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2018 Apr;55(4):3301-3315. doi: 10.1007/s12035-017-0564-9. Epub 
      2017 May 9.