Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists have demonstrated therapeutic properties for several brain disorders, including alcohol dependence. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated and little is known about their effects in the brain. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar and fenofibrate decreased ethanol consumption in male C57BL/6J mice while bezafibrate did not. Hypothesizing that fenofibrate and tesaglitazar are causing brain gene expression changes that precipitate the reduction in ethanol drinking, we gave daily oral injections of fenofibrate, tesaglitazar and bezafibrate to mice for eight consecutive days and collected liver, prefrontal cortex and amygdala 24 hours after last injection. RNA was isolated and purified using MagMAX-96 Total RNA Isolation Kit. Biotinylated, amplified cRNA was generated using Illumina TotalPrep RNA Amplification Kit and hybridized to Illumina MouseWG-6 v2.0 Expression microarrays.
PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption.
Sex, Specimen part
View SamplesInnate immune responses contributed to the containment of intestinal microbes.
Constitutive Immune Activity Promotes Tumorigenesis in Drosophila Intestinal Progenitor Cells.
Specimen part
View SamplesAction of alcohol on synaptic mRNA in the amygdala of mice
The synaptoneurosome transcriptome: a model for profiling the emolecular effects of alcohol.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part, Subject
View SamplesT lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part
View SamplesT lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part
View SamplesIn these studies we have for the first time described the transcriptome of the rat SFO, and have in addition identified genes the expression of which is significantly modified by either water or food deprivation.
Microarray analysis of the transcriptome of the subfornical organ in the rat: regulation by fluid and food deprivation.
Sex, Specimen part
View SamplesThe purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.
Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.
Sex, Age, Specimen part
View SamplesTo try to investigate the mechanism behind the adaptive phenotypes observed in a mice model model of HD crossed with mGluR5 knockout, we analyzed whether mutated huntingtin (Htt) expression in a mGluR5 null background could be altering the expression of genes that might be involved in the pattern of Htt aggregation and HD-related locomotor alterations.
Metabotropic glutamate receptor 5 knockout promotes motor and biochemical alterations in a mouse model of Huntington's disease.
Age, Specimen part
View SamplesMicroRNAs (miRNAs) are single-stranded non-coding RNAs that negatively regulate target gene expression through mRNA cleavage or translational repression. There is mounting evidence that they play critical roles in heart disease. The expression of known miRNAs in the heart has been studied at length by microarray and quantitative PCR but it is becoming evident that microRNA isoforms (isomiRs) are potentially physiologically important. It is well known that left ventricular (patho)physiology is influenced by transmural heterogeneity of cardiomyocyte phenotype, and this likely reflects underlying heterogeneity of gene expression. Given the significant role of miRNAs in regulating gene expression, knowledge of how the miRNA profile varies across the ventricular wall will be crucial to better understand the mechanisms governing transmural physiological heterogeneity. To determinine miRNA/isomiR expression profiles in the rat heart we investigated tissue from different locations across the left ventricular wall using deep sequencing. We detected significant quantities of 145 known rat miRNAs and 68 potential novel orthologs of known miRNAs, in mature, mature* and isomiR formation. Many isomiRs were detected at a higher frequency than their canonical sequence in miRBase and have different predicted targets. The most common miR-133a isomiR was more effective at targeting a construct containing a sequence from the gelsolin gene than was canonical miR-133a, as determined by dual-fluorescence assay. We identified a novel rat miR-1 homolog from a second miR-1 gene; and a novel rat miRNA similar to miR-676. We also cloned and sequenced the rat miR-486 gene which is not in miRBase (v18). Signalling pathways predicted to be targeted by the most highly detected miRNAs include Ubiquitin-mediated Proteolysis, Mitogen-Activated Protein Kinase, Regulation of Actin Cytoskeleton, Wnt signalling, Calcium Signalling, Gap junctions and Arrhythmogenic Right Ventricular Cardiomyopathy. Most miRNAs are not expressed in a gradient across the ventricular wall, with exceptions including miR-10b, miR-21, miR-99b and miR-486. Overall design: The hearts of 3 male 8 month old Sprague-Dawley rats were rapidly extracted after euthanasia with sodium pentobarbital. A section of the free wall of the left ventricle was dissected into epicardium, mid-myocardium and endocardium by cutting approximately 1 mm from the epicardial and endocardial surfaces. Small RNA was extracted (miRNeasy Kit; Qiagen, Crawley UK), quantified (Nanodrop; Thermo Scientific) and quality assessed for degradation (RNA Nano Chip, Bioanalyser 2100; Aligent Technologies, Wokingham UK; only samples with a RNA integrity no. (RIN) =8 were carried forward) and retention of small RNA (Small RNA Chip, Bioanalyser 2100). Small RNA was preferentially ligated with adapters, reverse transcribed into cDNA and amplified with 9 individually tagged primer indices (TruSeq Small RNA Sample Preparation Kit; Illumina, Little Chesterford, UK) and a library of small RNA created for each sample. After gel purification the cDNA products were again analysed on the bioanalyser using a High Sensitivity DNA Chip and assessed for the presence and concentration of the peak corresponding to ligated and tagged miRNA (approximately 147nt). Only samples with suitable RIN values exhibiting good retention of small RNA species were used for library preparation. After pooling, the samples were sequenced by TrinSeq (Trinity Genome Sequencing Lab & Neuropsychiatric Genetics Group, Trinity College Dublin, Ireland (http://www.medicine.tcd.ie/sequencing); using TruSeq SR Cluster Kit v5 (Illumina) and the resultant data trimmed and aligned to miRBase v18 (CLC Genomics Workbench v4.0; CLC bio, Swansea UK).
Distinctive profile of IsomiR expression and novel microRNAs in rat heart left ventricle.
No sample metadata fields
View Samples