Antidepressant-like actions by silencing of neuronal ELAV-like RNA-binding proteins HuB and HuC in a model of depression in male mice

摘要: Currently available antidepressant drugs often fail to achieve full remission and patients might evolve treatment resistance, showing the need a better therapy of depressive disorders. Increasing evidence supports that post-transcriptional regulation gene expression is important in neuronal development survival relevant role played by RNA binding proteins (RBP). To explore new therapeutic strategies, we investigated neuron-specific ELAV-like RBP (HuB, HuC, HuD) mouse model depression. In this study, 4-week unpredictable chronic mild stress (UCMS) protocol was applied mice induce depressive-like phenotype. last 2 weeks UCMS regimen, silencing HuB, HuC or HuD performed using specific antisense oligonucleotides (aODN). Treatment UCMS-exposed with anti-HuB anti-HuC aODN improved both anhedonia behavioural despair, used as measures behaviour, without modifying response stressed an anxiety-inducing environment. On contrary, promoted anxiolytic-like behaviour improving behaviours. The antidepressant-like phenotype not shown concurrently promotion adult hippocampal neurogenesis dentate gyrus, no increase BDNF CREB content detected. Conversely, CA3 region, projection area newly born neurons, HuB increased number BrdU/NeuN positive cells. These results give first indication nELAV modulation emotional states