PMID- 25639236
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20181215
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 33
IP  - 5
DP  - 2015 May
TI  - Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation 
      Deficits in MeCP2-Deficient Neurons.
PG  - 1618-29
LID - 10.1002/stem.1950 [doi]
AB  - In both the embryonic and adult brain, a critical step in neurogenesis is 
      neuronal maturation. Deficiency of MeCP2 leads to Rett syndrome, a severe 
      neurodevelopmental disorder. We have previously shown that MeCP2 plays critical 
      roles in the maturation step of new neurons during neurogenesis. MeCP2 is known 
      to regulate the expression of brain-derived neurotrophic factor (BDNF), a potent 
      neurotrophic factor for neuronal maturation. Nevertheless, how MeCP2 regulates 
      BDNF expression and how MeCP2 deficiency leads to reduced BDNF expression remain 
      unclear. Here, we show that MeCP2 regulates the expression of a microRNA, 
      miR-15a. We find that miR-15a plays a significant role in the regulation of 
      neuronal maturation. Overexpression of miR-15a inhibits dendritic morphogenesis 
      in immature neurons. Conversely, a reduction in miR-15a has the opposite effect. 
      We further show that miR-15a regulates expression levels of BDNF, and exogenous 
      BDNF could partially rescue the neuronal maturation deficits resulting from 
      miR-15a overexpression. Finally, inhibition of miR-15a could rescue neuronal 
      maturation deficits in MeCP2-deficient adult-born new neurons. These results 
      demonstrate a novel role for miR-15a in neuronal development and provide a 
      missing link in the regulation of BDNF by MeCP2.
CI  - (c) 2015 AlphaMed Press.
FAU - Gao, Yu
AU  - Gao Y
AD  - Waisman Center, School of Medicine and Public Health, Waisman Center, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Neuroscience, School 
      of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, 
      Madison, Wisconsin, USA.
FAU - Su, Juan
AU  - Su J
FAU - Guo, Weixiang
AU  - Guo W
FAU - Polich, Eric D
AU  - Polich ED
FAU - Magyar, Daniel P
AU  - Magyar DP
FAU - Xing, Yina
AU  - Xing Y
FAU - Li, Hongda
AU  - Li H
FAU - Smrt, Richard D
AU  - Smrt RD
FAU - Chang, Qiang
AU  - Chang Q
FAU - Zhao, Xinyu
AU  - Zhao X
LA  - eng
GR  - P30 HD003352/HD/NICHD NIH HHS/United States
GR  - R01 HD064743/HD/NICHD NIH HHS/United States
GR  - R01 MH080434/MH/NIMH NIH HHS/United States
GR  - R21 NS095632/NS/NINDS NIH HHS/United States
GR  - R01 MH078972/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn15 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cell Differentiation/genetics
MH  - Dendrites/*metabolism
MH  - Gene Expression Regulation
MH  - Hippocampus/pathology
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/*deficiency/metabolism
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Models, Biological
MH  - Mutation/genetics
PMC - PMC4409556
MID - NIHMS671828
OTO - NOTNLM
OT  - MeCP2
OT  - Neuron
OT  - Rett syndrome
OT  - dendrite
OT  - miRNA
OT  - neuronal Maturation
COIS- CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.
EDAT- 2015/02/03 06:00
MHDA- 2016/03/29 06:00
PMCR- 2016/05/01
CRDT- 2015/02/03 06:00
PHST- 2014/04/21 00:00 [received]
PHST- 2014/12/18 00:00 [accepted]
PHST- 2015/02/03 06:00 [entrez]
PHST- 2015/02/03 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1002/stem.1950 [doi]
PST - ppublish
SO  - Stem Cells. 2015 May;33(5):1618-29. doi: 10.1002/stem.1950.