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      Molecular Mechanism for Stress-Induced Depression Assessed by Sequencing miRNA and mRNA in Medial Prefrontal Cortex

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          Abstract

          Background

          Major depression is a prevalent mood disorder. Chronic stress is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stresses to neuronal atrophy remain elusive, which we have studied in the medial prefrontal cortices from depression mice.

          Methods and Results

          The mice were treated by the chronic unpredictable mild stress (CUMS) until they expressed depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. High-throughput sequencings of microRNA and mRNA in the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to demonstrate the molecular profiles of major depression. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated.

          Conclusion

          The deteriorations of GABAergic and dopaminergic synapses as well as axonal growth are associated with CUMS-induced depression.

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          Most cited references64

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          Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

          Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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            Behavioural despair in rats: a new model sensitive to antidepressant treatments.

            Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
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              • Abstract: found
              • Article: found
              Is Open Access

              Transcriptome-wide discovery of circular RNAs in Archaea

              Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 July 2016
                2016
                : 11
                : 7
                : e0159093
                Affiliations
                [1 ]Qingdao University, School of Pharmacy, Shandong, China
                [2 ]State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
                [3 ]University of Chinese Academy of Sciences, Beijing, China
                [4 ]College of Life Science, University of Science and Technology of China, Hefei, Anhui, China
                Chiba University Center for Forensic Mental Health, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JHW. Performed the experiments: KM LG AX SC. Analyzed the data: KM LG AX SC. Contributed reagents/materials/analysis tools: KM LG AX SC. Wrote the paper: JHW. Approved the final version of the manuscript: JHW KM LG AX SC.

                Article
                PONE-D-16-12992
                10.1371/journal.pone.0159093
                4948880
                27427907
                f8977bd6-3920-4594-a9a9-bf0f477281b5
                © 2016 Ma et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 March 2016
                : 27 June 2016
                Page count
                Figures: 2, Tables: 5, Pages: 21
                Funding
                Funded by: National Basic Research Program
                Award ID: 2013CB531304
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007847, Natural Science Foundation of Jilin Province;
                Award ID: 81471123
                Award Recipient :
                This study is granted by the National Basic Research Program (2013CB531304) and Natural Science Foundation China (81471123) to JHW.
                Categories
                Research Article
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                MicroRNAs
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                MicroRNAs
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Messenger RNA
                Biology and life sciences
                Molecular biology
                Molecular biology techniques
                Sequencing techniques
                RNA sequencing
                Research and analysis methods
                Molecular biology techniques
                Sequencing techniques
                RNA sequencing
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rodents
                Mice
                Biology and Life Sciences
                Anatomy
                Nervous System
                Synapses
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Synapses
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Neurophysiology
                Synapses
                Medicine and Health Sciences
                Physiology
                Electrophysiology
                Neurophysiology
                Synapses
                Biology and Life Sciences
                Neuroscience
                Neurophysiology
                Synapses
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Anatomy
                Brain
                Prefrontal Cortex
                Medicine and Health Sciences
                Anatomy
                Brain
                Prefrontal Cortex
                Custom metadata
                The authors have registered with Genebank with the code GSE81590 to access their transcriptome and microRNA expression profiles.

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