PMID- 25079084
OWN - NLM
STAT- MEDLINE
DCOM- 20150409
LR  - 20220410
IS  - 1488-2434 (Electronic)
IS  - 1180-4882 (Print)
IS  - 1180-4882 (Linking)
VI  - 39
IP  - 5
DP  - 2014 Sep
TI  - BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the 
      effects of oleanolic acid in male mice.
PG  - 348-59
AB  - BACKGROUND: Although previous study has demonstrated that brain-derived 
      neurotrophic factor (BDNF) is involved in the antidepressant-like effect of 
      oleanolic acid, there is little information regarding the details of the 
      molecular mechanism involved in this effect. METHODS: We used a chronic 
      unpredictable mild stress (CUMS) model to test the antidepressant-like effect of 
      oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic 
      protein expression in the male mouse hippocampus. Furthermore, we explored the 
      possible signalling pathways associated with miR-132 expression that mediate the 
      effect of oleanolic acid on neuronal proliferation. RESULTS: The results 
      demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced 
      anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid 
      led to the BDNF-related phosphorylation and activation of extracellular 
      signal-regulated kinases (ERK) and cyclic adenosine monophosphate response 
      element binding protein (CREB), which was associated with the upregulation of 
      miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an 
      miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal 
      proliferation and the postsynaptic density protein 95, but did not affect 
      presynaptic protein synapsin I. LIMITATIONS: Several other stimuli can also 
      induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may 
      not be restricted to neurotrophic signalling. CONCLUSION: Our results show that 
      oleanolic acid induces the upregulation of miR-132, which serves as an important 
      regulator of neurotrophic actions, mainly through the activation of the 
      hippocampal BDNF-ERK-CREB signalling pathways.
FAU - Yi, Li-Tao
AU  - Yi LT
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
FAU - Li, Jing
AU  - Li J
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
FAU - Liu, Bin-Bin
AU  - Liu BB
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
FAU - Luo, Liu
AU  - Luo L
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
FAU - Liu, Qing
AU  - Liu Q
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
FAU - Geng, Di
AU  - Geng D
AD  - The Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen, Fujian Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Psychiatry Neurosci
JT  - Journal of psychiatry & neuroscience : JPN
JID - 9107859
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (MIRN132 microRNA, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.4.8 (Guanylate Kinases)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Chronic Disease
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Depressive Disorder/drug therapy/physiopathology
MH  - Disease Models, Animal
MH  - Disks Large Homolog 4 Protein
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Guanylate Kinases/metabolism
MH  - Hippocampus/drug effects/physiopathology
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Mice, Inbred ICR
MH  - MicroRNAs/*metabolism
MH  - Neurogenesis/drug effects/physiology
MH  - Neurons/drug effects/physiology
MH  - Oleanolic Acid/*pharmacology
MH  - Random Allocation
MH  - Signal Transduction/drug effects
MH  - Stress, Psychological
MH  - Uncertainty
MH  - Up-Regulation/drug effects
PMC - PMC4160364
EDAT- 2014/08/01 06:00
MHDA- 2015/04/10 06:00
PMCR- 2014/09/01
CRDT- 2014/08/01 06:00
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/04/10 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1503/jpn.130169 [pii]
AID - jpn-39-348 [pii]
AID - 10.1503/jpn.130169 [doi]
PST - ppublish
SO  - J Psychiatry Neurosci. 2014 Sep;39(5):348-59. doi: 10.1503/jpn.130169.