miR-409 and miR-411 Modulation in the Adult Brain of a Rat Model of Depression and After Fluoxetine Treatment.

ABSTRACT

Depression is a chronic debilitating disorder predicted to affect around 20% of the world population. Both brain and peripheral changes, including neuroplastic changes have been shown to occur in the brains of depressed individuals and animal models of depression. Over the past few decades, growing evidence has supported the role of miRNAs as regulators of critical aspects of brain plasticity and function, namely in the context of depression. These molecules are not only highly expressed in the brain, but are also relatively stable in bodily fluids, including blood. Previous microarray analysis from our group has disclosed molecular players in the hippocampal dentate gyrus (DG), in the context of depression and antidepressant treatment. Two miRNAs in particular-miR-409-5p and miR-411-5p-were significantly up-regulated in the DG of an unpredictable chronic mild stress (CMS) rat model of depression and reversed by antidepressant treatment. Here, we further analyzed the levels of these miRNAs along the DG longitudinal axis and in other brain regions involved in the pathophysiology of depression, as well as in peripheral blood of CMS-exposed rats and after fluoxetine treatment. The effects of CMS and fluoxetine treatment on miR-409-5p and miR-411-5p levels varied across brain regions, and miR-411-5p was significantly decreased in the blood of fluoxetine-treated rats. Additional bioinformatic analyses revealed target genes and pathways of these miRNAs related to neurotransmitter signaling and neuroplasticity functions; an implication of the two miRNAs in the regulation of the cellular and molecular changes observed in these brain regions in depression is worth further examination.