Project description:MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. We report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex, and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. Here, we performed small RNA Sequencing of mouse basolateral amygdala after miR15a knockdown using injection of a miR-15a sponge virus or control sponge virus.
Project description:MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. Here, we report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. In humans, pharmacological activation of the glucocorticoid receptor, as well as exposure to childhood trauma, was associated with increased microRNA-15a levels in peripheral blood. Taken together, our results support an important role for microRNA-15a in stress adaptation and the pathogenesis of stress-related psychopathologies.
Project description:While microRNAs (miRs) have been extensively studied in the context of malignancy and tumor progression, their functions in regulating T cell activation are less clear. We found reduced levels of miR-15a/16 at 3-18 h post-T cell receptor (TCR) stimulation, suggesting a role in shaping T cell activation. An inducible miR15a/16 transgenic mouse model was developed to determine how elevating miR-15a/16 levels during early stages of activation would affect T cell proliferation and to identify TCR signaling pathways regulated by this miR pair. Doxycyclin (DOX) induced expression of miR-15a/16 from 0-18 h post-TCR stimulation decreased ex vivo proliferation as well as in vivo antigen-specific proliferation. Bioinformatic and proteomic approaches were combined to identify MEK1 as a target of miR-15a/16. MEK1 targeting by miR-15a/16 was confirmed using miR mimics that decreased MEK1 containing the 3’-UTR target nucleotide sequence (UGCUGCUA) but did not decrease MEK1 containing a mutated control sequence (AAAAAAAA). Phosphorylation of downstream signaling molecules ERK1/2 and Elk1 were decreased with DOX-induced miR-15a/16 expression. In addition to MEK1, ERK1 was subsequently found to be targeted by miR-15a/16, with DOX induced miR-15a/16 reducing total ERK1 levels in T cells. These findings show that TCR stimulation reduces miR-15a/16 levels at early stages of T cell activation to facilitate increased MEK1 and ERK1, and this promotes sustained MEK1-ERK1/2-Elk1 signaling required for optimal proliferation.
Project description:According to the Mainz Coping Inventory (MCI) (Krohne & Egloff, 1999) people use four main strategies for coping (i.e. Non-defensive, Repressing, High-Anxious and Sensitizing). To bridge the gap between psychology and genetics, the Affymetrix GeneChip miRNA 3.0 Array (Affymetrix, Santa Clara, USA) was used to analyze blood plasma of healthy male individuals with differing MCI coping styles to gain miRNA profiles associated with the MCI assessment and to predict biomarkers for the MCI coping modes.
Project description:We intended to investigate effects of mmu-miR-15a-3p on gene expression in mice We used microarrays to compare gene expression in mouse B/CMBA.Ov cell lines transfected with mmu-miR-15a-3p and negative control mimic
Project description:Given the tumor suppressing function of miR-15a/16-1 cluster, we studied its role in the germinal center B-cells that give rise to most lymphoid malignancies.
Project description:Individual stress coping style has profound effects on how animals respond to environmental change, and individuals within a population strikingly differ in how gene expression shifts in response to challenge. This study used a wild type Zebrafish (Danio rerio) population to: 1) identify and screen for individual coping style using a screening protocol for risk taking in groups and 2) do global transcriptomics of brains from proactive, reactive or randomly chosen individuals (n=10/group) under control conditions. Results show that within our population proactive and reactive individual coping styles can be accurately identified and may represent 10-30% of individuals within the population. Microarray data analyses identify fundamental differences between the three different groups where variance in gene expression values are reduced by using coping style as an explanatory variable. Furthermore, significant differences in mRNAs and related biological processes suggest that even under identical environmental conditions the molecular mechanisms that underpin physiological processes are very different between proactive and reactive individuals within a population.