Transcriptome analyses reveal enrichment of specific lncRNAs in specific brain regions and neuronal populations
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61401 | GEO | 2015/03/06
SECONDARY ACCESSION(S): PRJNA260988
REPOSITORIES: GEO
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2017-10-06 | E-MTAB-5995 | biostudies-arrayexpress
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
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Project description:In this research, we investigated the abnormal expression of lncRNA and established lncRNA-associated ceRNA regulatory networks composed of potential therapeutic targets in AD based on RNA sequencing (RNA-seq) analysis and experimental verification. RNA-seq was performed in the cerebral cortex and hippocampus of 5×FAD mice of AD to systematically investigate altered lncRNA-associated ceRNA regulatory network, along with qualitative analyses for key differentially expressed lncRNAs, miRNAs, and mRNAs involved. The results showed that 7 lncRNAs were significantly altered in the cortex and hippocampus of 5×FAD mice compared with WT mice. The potential functions of differentially expressed genes were highly correlated with learning and memory activities and the pathogenesis of AD. Furthermore, lncRNA Xist and highly correlated miRNAs and mRNAs were identified as key mediators of pathophysiological processes in AD. Our findings illustrated the AD-derived lncRNA-mediated ceRNA network, accompanied by aberrant expression involved in the pathological gene networks, which may contribute to understanding the pathological mechanism of AD and provide potential therapeutic targets for drug development.
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Project description:LncRNA expression profiling for liver tissues of mice fed for NFD, LSF and HSF groups Summary: An abstract of the experiment and the data analysis. Experiment Workflow: A workflow of the experiment and the data analysis. Project Description: Sample and experiment information. Array Information: Mouse 8 x 60K LncRNA expression array information. Summary Table of Files for Data Delivery: Contains summary table of files for data delivery and the recommended software programs for viewing the data. Data Analysis for LncRNAs 1. Raw LncRNA data normalization and low intensity filtering: Raw signal intensities were normalized in quantile method by GeneSpring GX v11.5.1, and low intensity LncRNAs were filtered (LncRNAs that at least 6 out of 9 samples have flags in Present or Marginal were chosen for further analysis, these LncRNAs can be found from the LncRNA Expression Profiling Data.xls file). 2. Quality assessment of LncRNA data after filtering: Contains Box Plot and Scatter Plot for LncRNAs after filtering (This data can be found from the LncRNA Expression Profiling Data.xls file). 3. Differentially expressed LncRNAs screening: Contains differentially expressed genes with statistical significance that passed Volcano Plot filtering (Fold Change >= 2.0, P-value <= 0.05) (This data can be found from the Differentially Expressed LncRNAs.xls file). 4. Heat Map and Hierarchical Clustering: Hierarchical Clustering of Differentially Expressed LncRNAs (The heat map can be found from the LncRNA Expression Profiling Data.xls file). Data Analysis for mRNAs 1. Raw mRNA data normalization and low intensity filtering: Raw signal intensities were normalized in quantile method by GeneSpring GX v11.5.1, and low intensity mRNAs were filtered (mRNAs that at least 6 out of 9 samples have flags in Present or Marginal were chosen for further analysis, these mRNAs can be found from the mRNA Expression Profiling Data.xls file). 2. Quality assessment of mRNA data after filtering: Contains Box Plot and Scatter Plot for mRNAs after filtering (This data can be found from the mRNA Expression Profiling Data.xls file). 3. Differentially expressed mRNAs screening: Contains differentially expressed genes with statistical significance that passed Volcano Plot filtering (Fold Change >= 2.0, P-value <= 0.05) (This data can be found from the Differentially Expressed mRNAs.xls file). 4. Heat Map and Hierarchical Clustering: Hierarchical Clustering of Differentially Expressed mRNAs (The heat map can be found from the mRNA Expression Profiling Data.xls file). 5. Pathway analysis: Pathway analysis of the differentially expressed mRNAs. 6. GO analysis: GO term analysis of the differentially expressed mRNAs. LncRNA Classification and Subgroup Analysis 1. Rinn lincRNAs profiling: Contains profiling data of all lincRNAs based on John Rinn's papers (This data can be found from the Rinn lincRNAs profiling.xls file). 2. LincRNAs nearby coding gene data table: Contains the differentially expressed lincRNAs and nearby coding gene pairs (distance < 300 kb) (This data can be found from the LincRNAs nearby coding gene data table.xls file). Sample RNA Quality Control: Sample quality control data file from NanoDrop ND-1000 spectrophotometer and standard denaturing agarose gel electrophoresis. Methods: A brief introduction of methods for sample preparation, microarray design, experiment, and data analysis.
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| EGAS00001003922 | EGA