PMID- 26239616
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20150924
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 12
IP  - 4
DP  - 2015 Oct
TI  - MeCP2 controls hippocampal brain-derived neurotrophic factor expression via 
      homeostatic interactions with microRNA‑132 in rats with depression.
PG  - 5399-406
LID - 10.3892/mmr.2015.4104 [doi]
AB  - Major depressive disorder (MDD) is a considerable public health concern, which 
      affects patients worldwide. MDD is associated with psychosocial impairment, poor 
      quality of life, and significant disability, morbidity and mortality. Stress is a 
      major factor in depression, which impairs the structural and functional 
      plasticity of the hippocampus. Previous studies have demonstrated that chronic 
      unpredictable mild stress is able to downregulate the expression of brain‑derived 
      neurotrophic factor (BDNF) and methyl‑CpG‑binding protein 2 (MeCP2), and alter 
      the expression levels of certain microRNAs (miR). The aim of the present study 
      was to investigate the regulatory association between BDNF, MeCP2 and miR-132 in 
      an animal model of chronic stress‑induced depression. ELISA, western blot and 
      qPCR were used to detect the expression levels of BDNF, MeCP2 and miR-132 in the 
      peripheral blood samples of patients with MDD and in the hippocampi of depressed 
      animals. In addition, a dual luciferase reporter gene system was used to 
      determine whether miR-132 directly targets BDNF or MeCP2. The present study 
      demonstrated that, as compared with normal subjects, miR‑132 expression was 
      increased in the peripheral blood samples of patients with MDD, whereas the 
      expression of MeCP2 and BDNF was decreased; thus, the expression levels of MeCP2 
      and BDNF were negatively correlated with those of miR‑132. In addition, in an 
      animal model of chronic stress‑induced depression, increased expression levels of 
      miR‑132, and decreased levels of MeCP2 and BDNF were detected in the hippocampi. 
      Furthermore, knockdown of MeCP2 expression in primary hippocampal neurons 
      increased the expression of miR‑132 and decreased the expression levels of BDNF. 
      The results of the present study demonstrated that miR‑132 may directly target 
      MeCP2, but not BDNF, and control its expression at the transcriptional and 
      translational level. miR‑132 was also shown to negatively regulate BDNF 
      expression. The reduced expression levels of BDNF, as induced by MeCP2 knockdown, 
      were enhanced by miR‑132 mimics, and were rescued by miR‑132 inhibitors. These 
      results suggested that homeostatic interactions between MeCP2 and miR‑132 may 
      regulate hippocampal BDNF levels, which may have a role in the pathogenesis of 
      MDD.
FAU - Su, Meilei
AU  - Su M
AD  - Department of Psychology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Hong, Jun
AU  - Hong J
AD  - Department of Psychology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Zhao, Yongzhi
AU  - Zhao Y
AD  - Department of Psychology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Liu, Shuai
AU  - Liu S
AD  - Department of Psychology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Xue, Xiang
AU  - Xue X
AD  - Department of Psychology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20150720
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MIRN132 microRNA, rat)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (MicroRNAs)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/blood/*genetics/metabolism
MH  - Case-Control Studies
MH  - Corticosterone/blood
MH  - Depression/*genetics/metabolism
MH  - Depressive Disorder, Major/genetics/metabolism
MH  - Disease Models, Animal
MH  - *Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Hippocampus/*metabolism
MH  - Homeostasis
MH  - Humans
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/blood/genetics/*metabolism
MH  - MicroRNAs/*genetics
MH  - RNA Interference
MH  - Rats
MH  - Stress, Physiological
EDAT- 2015/08/05 06:00
MHDA- 2016/06/28 06:00
CRDT- 2015/08/05 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2015/06/03 00:00 [accepted]
PHST- 2015/08/05 06:00 [entrez]
PHST- 2015/08/05 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
AID - 10.3892/mmr.2015.4104 [doi]
PST - ppublish
SO  - Mol Med Rep. 2015 Oct;12(4):5399-406. doi: 10.3892/mmr.2015.4104. Epub 2015 Jul 
      20.