title: BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice.
abstract: 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.
  
  
  CONCLUSIONS
  Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling.
  
  
  CONCLUSIONS
  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.
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Li-Tao
authors: LT
authors: Yi
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Jing
authors: J
authors: Li
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Bin-Bin
authors: BB
authors: Liu
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Liu
authors: L
authors: Luo
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Qing
authors: Q
authors: Liu
authors: The Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, China.
authors: Di
authors: D
authors: Geng
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002908:Chronic Disease; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009828:Oleanolic Acid / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological; D035501:Uncertainty; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C546976:MIRN132 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D009828:Oleanolic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D051528:Guanylate Kinases