BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

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. © 2014 canadian medical association.