Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances.

Dysregulation of miR-185, miR-193a, and miR-450a in the skin are linked to the depressive phenotype.

Background: Dysregulated microRNAs (miRNAs) in dermal fibroblasts of depressive subjects, indicate biomarker potential and can possibly aid clinical diagnostics. To overcome methodological challenges related to human experiments and fibroblast cultures, we here validate 38 miRNAs previously observed to be dysregulated in human fibroblasts from depressed subjects, in the skin of four distinct rat models of depression.

Methods: In the presented study male rats from the adrenocorticotropic hormone (ACTH) model (n = 10/group), the chronic mild stress model (n = 10/group), Wistar Kyoto/Wistar Hannover rats (n = 10/group), and Flinders Resistant/Flinders Sensitive Line rats (n = 8/group) were included.

Efficient Knockdown and Lack of Passenger Strand Activity by Dicer-Independent shRNAs Expressed from Pol II-Driven MicroRNA Scaffolds.

The expression of short hairpin RNAs (shRNAs) may result in unwanted activity from the co-processed passenger strand. Recent studies have shown that shortening the stem of conventional shRNAs abolishes passenger strand release. These Dicer-independent shRNAs, expressed from RNA polymerase III (Pol III) promoters, rely on Ago2 processing in resemblance to miR-451.