MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis

Gene-Stress-Epigenetic Regulation of FKBP5: Clinical and Translational Implications.

Major depressive disorder (MDD) is a major public health concern. Despite tremendous advances, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by modulating translation, messenger RNA (mRNA) degradation, or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recent studies demonstrating the involvement of miRNAs in several aspects of neural plasticity, neurogenesis, and stress response, and more direct studies in human postmortem brain provide strong evidence that miRNAs can not only play a critical role in MDD pathogenesis, but can also open up new avenues for the development of therapeutic targets. Circulating miRNAs are now being considered as possible biomarkers in disease pathogenesis and in monitoring therapeutic responses because of the presence and/or release of miRNAs in blood cells as well as in other peripheral tissues. In this review, these aspects are discussed in a comprehensive and critical manner.

Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications.

Although the etiology and expression of psychiatric disorders are complex, mammals show biologically preserved behavioral and neurobiological responses to valent stimuli which underlie the use of rodent models of post-traumatic stress disorder (PTSD). PTSD is a complex phenotype that is difficult to model in rodents because it is diagnosed by patient interview and influenced by both environmental and genetic factors. However, given that PTSD results from traumatic experiences, rodent models can simulate stress induction and disorder development. By manipulating stress type, intensity, duration, and frequency, preclinical models reflect core PTSD phenotypes, measured through various behavioral assays. Paradigms precipitate the disorder by applying physical, social, and psychological stressors individually or in combination. This review discusses the methods used to trigger and evaluate PTSD-like phenotypes. It highlights studies employing each stress model and evaluates their translational efficacies against DSM-5, validity criteria, and criteria proposed by Yehuda and Antelman’s commentary in 1993. This is intended to aid in paradigm selection by informing readers about rodent models, their benefits to the clinical community, challenges associated with the translational models, and opportunities for future work. To inform PTSD model validity and relevance to human psychopathology, we propose that models incorporate behavioral test batteries, individual differences, sex differences, strain and stock differences, early life stress effects, biomarkers, stringent success criteria for drug development, Research Domain Criteria, technological advances, and cross-species comparisons. We conclude that, despite the challenges, animal studies will be pivotal to advances in understanding PTSD and the neurobiology of stress.

/pdf/rodent-models-of-post-traumatic-stress-disorder-behavioral-dqf9algfqm.pdf

Rodent models of post-traumatic stress disorder: behavioral assessment.

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients

MicroRNAs (miRNA) are a class of small noncoding RNAs that have recently emerged as epigenetic modulators of gene expression in psychiatric diseases like schizophrenia and major depression. So far, miRNAs have neither been studied in patients suffering from posttraumatic stress disorder (PTSD) nor in PTSD animal models. Here, we present the first study exploring the connection between miRNAs and PTSD. Employing our previously established PTSD mouse model, we assessed miRNA profiles in prefrontal cortices (PFCs) dissected from either fluoxetine or control-treated wildtype C57BL/6N mice 74 days after their subjection to either a single traumatic electric footshock or mock-treatment. Fluoxetine is an antidepressant known to be effective both in PTSD patients and in mice suffering from a PTSD-like syndrome. Screening for differences in the relative expression levels of all potential miRNA target sequences of miRBase 18.0 by pairwise comparison of the PFC miRNA profiles of the four mouse groups mentioned resulted in identification of five miRNA candidate molecules. Validation of these miRNA candidates by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) revealed that the therapeutic action of fluoxetine in shocked mice is associated with a significant reduction in mmu-miR-1971 expression. Furthermore, our findings suggest that traumatic stress and fluoxetine interact to cause distinct alterations in the mouse PFC miRNA signature in the long-term.

/pdf/therapeutic-action-of-fluoxetine-is-associated-with-a-48y4ppymlv.pdf

Therapeutic Action of Fluoxetine is Associated with a Reduction in Prefrontal Cortical miR-1971 Expression Levels in a Mouse Model of Posttraumatic Stress Disorder.

A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies.

39P ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein with potent CD8 T cell and NK cell stimulating capacity that shows additive efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity

Christine Huber

Papers

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients

Therapeutic Action of Fluoxetine is Associated with a Reduction in Prefrontal Cortical miR-1971 Expression Levels in a Mouse Model of Posttraumatic Stress Disorder.

A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies.

39P ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein with potent CD8 T cell and NK cell stimulating capacity that shows additive efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity