Early and time dependent effects of antidepressant treatments on rat hippocampal miRNome

MicroRNAs have recently emerged as key regulators of gene/protein expression modulation in the brain, where they have a crucial role in the regulation of neurogenesis, neuronal differentiation, survival, and neuroplasticity. Studies have begun to show that miRNAs could be involved in the pathophysiology of mood disorders and in the action of some psychotropics, but much remains to be uncovered [1,2]. To the best of our knowledge, thus far no studies have investigated the temporal effects of antidepressant treatments on the whole hippocampal miRNome. Therefore, main aim of the present work was to verify whether and how short- and long-term treatments with three different antide- pressants, desipramine, fluoxetine and agomelatine, could affect rat hippocampal miRNome. We found that, although in a specific way, all antidepressants induced early and time-dependent mod- ifications in microRNA expression, with more marked effects of agomelatine after 3 days, of fluoxetine after 7 and of desipramine after 14 days. Interestingly, some of the miRNAs were found to be similarly affected by different antidepressants, thus suggesting common effects. Bioinformatic analysis highlighted enrichment of microRNA targets in different pathways, some related to neuronal functions previously associated to pathophysiology and pharmaco- therapy, and others, particularly at early times to gene transcription and epigenetic mechanisms. Moreover, we validated changes in the expression of some putative target genes, which could be of interest in unraveling antidepressant mechanism. Overall, our data support a role for microRNAs as early mediators of antidepressant effects and open new options in the research for better therapies for mood disorders.