Expression Profiling of a Genetic Animal Model of Depression
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Adam Taylor
PROVIDER: E-GEOD-20388 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.
Blaveri Ekaterini E Kelly Fiona F Mallei Alessandra A Harris Kriss K Taylor Adam A Reid Juliet J Razzoli Maria M Carboni Lucia L Piubelli Chiara C Musazzi Laura L Racagni Girogio G Mathé Aleksander A Popoli Maurizio M Domenici Enrico E Bates Stewart S
PloS one 20100907 9
<h4>Background</h4>The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.<h4>Principal findings</h4>In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL) and control Flinders Depression Resistant (FRL) lines to understand molecular basis for the diff ...[more]
Similar Datasets
Project description:Expression Profiling of a Genetic Animal Model of Depression Reveals Novel Molecular Pathways Underlying Depressive-like Behaviours In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL) and control Flinders Depression Resistant (FRL) lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model.
2010-04-01 | GSE20388 | GEO
Project description:Induced sputum is used to sample inflammatory cells, predominantly neutrophils and macrophages, from the airways of COPD patients. Our aim was to identify candidate genes associated with the degree of airflow obstruction and the extent of emphysema by expression profiling, and then to confirm these findings for selected candidates using specific PCR and protein analysis. Two sputum studies were performed in GOLD stage 2 -4 COPD ex-smokers from the ECLIPSE cohort. First, gene array profiling at baseline in 1480 patients was performed. At year 1, samples from a separate population of 176 patients were used for real-time PCR. The gene expression findings for IL-18R were further analysed using immunohistochemistry in lung tissue and induced sputum samples from patients outside the ECLIPSE cohort.
2010-06-16 | E-GEOD-22148 | biostudies-arrayexpress
Project description:Being able to identify patients in whom immunological tolerance has been established or is developing would allow an individually tailored approach to post-transplant management of kidney allograft recipients. Ex vivo immunological monitoring was performed on samples from five groups of European renal transplant recipients (“IOT samples”): ten drug-free tolerant recipients who were functionally stable despite remaining immunosuppression-free for more than one year (Tol-DF); also functionally stable patients on minimal immunosuppression (<10 mg/day prednisone, s-LP); stable patients maintained with calcineurin inhibitors (s-CNI); stable patients maintained on CNI-free immunosuppression regimen (s-nCNI); patients showing signs of chronic rejection (CR) and healthy controls (HC). Among the investigation of other biomarkers and bioassays, gene expression profiles were generated on custom Agilent 8x15K 60mer oligonucleotide microarrays (“RISET 2.0”) on the IOT cohort (training set) and on an independent cohort of patients from the ITN (USA) that contained similar groups of patients and included 23 tolerant recipients (“ITN samples”, test set). Set of genes were identified, whose expression on whole blood allowed the identification of 100% of the tolerant recipients in the training set and 84% in the test set. Keywords: classification of clinical samples, tolerance prediction IOT samples: 13 samples from 10 Tol-DF patients, 16 samples from 11 s-LP patients, 8 samples from 8 s-nCNI patients, 40 samples from 28 s-CNI patients, 10 samples from 9 CR patients, and 8 samples from 8 HC donors were analysed on a custom Agilent 8x15K 60mer oligonucleotide microarray encomprising 5069 probes in triplicates. The microarray is dedicated to transplantation research and was designed based on current literature and published and unpublished data provided by the RISET consortium. For the probe selection procedure we specially focused on the detection of multiple transcript variants of a gene, on optimized hybridization properties of the probes, and on the avoidance of crosshybridization. The sampling dates of replicate samples from the same patient range from one day to 1.5 years. ITN samples: 31 samples from 23 Tol-DF patients, 14 samples from 11 s-LP patients, 52 samples from 34 s-CNI patients, 25 samples from 18 CR patients, and 20 samples from 20 HC donors were analysed on the same microarray platform and served as test set. The samples of the two cohorts differ in the protocol of RNA preparation.
2010-05-25 | E-GEOD-14655 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, reflecting the need for a better understanding of hepatocarcinogenesis. In this study, we examined the genome-wide expression profiles of both miRNAs and mRNAs from paired tumor and adjacent non-tumor tissues from a cohort of 96 HCC patients in Hong Kong where hepatitis B virus (HBV) is endemic. The comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that it is an important regulator for normal mitochondrial metabolism. A decreased level of miR-122 leads to an increase in expression of miR-122 seed-matched genes, a loss of mitochondrial metabolic function, and a decrease in the expression of many miR-122 secondary targets. These secondary targets are prognostic markers for HCC patients. Transcriptome profiling data from an additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. To test the HCC findings in normal mouse liver, we used an antagomir against miR-122 and identified altered gene expression profiling by microarray analysis in mouse in vivo experiments. The mouse data recapitulated the human HCC findings. Our anti-miR122 data further provided a direct link between increases in the mRNA levels of miR-122 controlled genes and impairments of mitochondrial metabolism. In summary, we find miR-122 loss may be detrimental to mitochondrial-related metabolisms in sustaining critical liver function and contribute to the morbidity and mortality of liver cancer patients. Mouse liver profiling: In one treatment regimen, four animals were given four doses of 100mg ASO/kg body weight, administered every other day, and sacrificed one day after the last dose. Four animals treated for four weeks were treated twice weekly with 50mg ASO/kg body weight, and sacrificed two days after the last dose. Mice were sacrificed in the morning, and liver was removed for further analysis. Samples from oligonucleotide-treated mice were referenced against samples from saline-treated mice in fluor-reversed pairs. Human liver profiling: For human HCC patient samples, 192 samples -- 96 resected tumor and 96 adjacent non-tumor liver tissues -- were collected from 96 patients who had undergone hepatectomy for curative treatment of HCC at Queen Mary Hospital, Pokfulam, Hong Kong between 1990 and 2007. Informed consents were obtained from patients regarding the use of the liver specimens for research. Samples were hybridized to Affymetrix arrays for mRNA profiling and were analyzed by quantitative PCR for microRNA profiling.
2010-06-09 | E-GEOD-22058 | biostudies-arrayexpress
Project description:Expression profiling of a cohort of mice was derived from a standard F2 intercross using two standard inbred strains, C57BL/6J and DBA/2J. In this study, we selected 127 male animals that had been raised on a standard rodent chow diet (Purina Chow from Ralston-Purina Co., St. Louis, MO) for eight weeks and then switched to a high fat diet for sixteen additional weeks. At 20 weeks of age, the mice were euthanized and liver tissues were collected and flash frozen in liquid nitrogen and stored at -80 degrees C prior to RNA isolation. All procedures of housing and treatment of animals were performed in accordance with IACUC regulations. RNA preparation and array hybridizations were performed at Rosetta Inpharmatics. The custom ink-jet microarrays were manufactured by Agilent Technologies (Palo Alto, CA). A custom array was designed for this study and consisted of 39,280 non-control oligonuceotides extracted from the mouse Unigene clusters and combined with RefSeq sequences and RIKEN full-length cDNA clones. Arrays were quantified on the basis of spot intensity relative to background, adjusted for experimental variation between arrays using average intensity over multiple channels, and fitted to a previously described error model to determine significance (type I error).
2011-06-01 | E-GEOD-16886 | biostudies-arrayexpress
Project description:Toxicokinetic and metabolism studies are considered crucial to dose setting and interpretation of data from rodent carcinogenicity studies. The metabolism and distribution studies are usually conducted in 6 to 8 week old rodents. However cancer studies generally involve exposures from 6 weeks of age to 108 weeks or more of age. It is recognized that age-related differences in sensitivities to some xenobiotics occur in several rodent models including the rat. However, the potential for changes in metabolism with age has received little attention in the toxicology community especially in regard to extrapolation of rodent data to human risk assessment. The advent of microarray technology has allowed a more global assessment of genes whose products are associated with xenobiotic metabolism. We studied hepatic gene expression in 38 untreated F344/N rats at approximately 32, 58 and 84 weeks of age corresponding to 6, 12, and 18 months on study. Statistical analysis of microarray (SAM) identified differential expression between the youngest and the oldest rats for genes whose products are involved in phase I and phase II metabolic pathways. Fifteen of 30 cytochrome P450 genes from CYP families 1 â 4 showed marked decrease in expression at 84 weeks while only two showed increased expression. The results of this study demonstrate prominent decreased expression in CYP family genes involved in xenobiotic metabolism in untreated rats as they age. The assumption of a constant metabolic profile when extrapolating results from long-term chemical exposures needs to be reconsidered. Experiment Overall Design: Animals and Study Design. Male Fischer 344 rats approximately 36 ± 3 days old were supplied by Taconic laboratory animals (Germantown, NY) and were approximately six weeks old when placed in study rooms as sentinel animals for two-year studies. All studies were conducted at Battelle Science and Technology International (Columbus, Ohio). The livers from the male rat sentinels from three studies at six months (15 total rats), two studies at twelve months (10 total rats) and three studies at eighteen months (13 total rats) were used in this study. The sampling times corresponded to approximately 32, 58 and 84 weeks of age for the rats. The studies in which the sentinels were a part were approved by Battelleâs Institute Animal Care and Use Committee and were conducted in accordance with the guide for the care and use of laboratory animals (ILAR 1996). Details of the animal care and handling for studies conducted at Battelle have been reported previously (Boorman et al. 2005). Experiment Overall Design: The rats were kept in a cage until necropsy. The rats were anesthetized with CO2/O2, blood samples obtained for serology by cardiac puncture, the abdominal cavity was opened and the portal vein was severed. The left liver lobe was promptly removed and a cross section was placed in 10% neutral buffered formalin (NFB). The liver section was embedded, sectioned and stained with H&E and examined. The remainder of the left lobe was processed for subsequent RNA isolation. Experiment Overall Design: RNA isolation. The left hepatic lobe was cut into 0.5 cm cubes or smaller and immersed in RNALater® (Ambion, Austin, TX) within 4 minutes of necropsy. The tissues were stored in RNALater® overnight at 4+/-30C, then stored at - 20+/-10C until RNA isolation (within 60 days). Details of the RNA isolation procedures have been previous published (Boorman et al. 2005). Briefly, the RNA samples were frozen at - 700 C and shipped to the NTP repository until transfer to Paradigm Array Labs (Icoria, Inc., A Clinical Data Inc. Company, RTP, NC) for microarray analysis. RNA was isolated from individual rats. Equal amounts of RNA from sixty-three male sentinel rats (25 rats at 32 weeks of age, 25 rats at 58 weeks of age and 13 rats at 84 weeks of age) were used to form a composite control pool for comparison with the individual rats at each age. Experiment Overall Design: Microarray Hybridizations. One µg of total RNA from either an individual rat or from the pooled sample was amplified and labeled with a fluorescent dye (either Cy3 or Cy5) using the Low RNA Input Linear Amplification Labeling kit (Agilent Technologies, Palo Alto, CA) following the manufacturerâs protocol. The amount and quality of the resulting fluorescently labeled cRNA was assessed using a Nanodrop ND-100 spectrophometer and an Agilent Bioanalyzer. Equal amounts of Cy3- or Cy5-labeled cRNA were hybridized to the Agilent Rat Oligo Microarray (Agilent Technologies, Inc., Palo Alto, CA) for 17 hrs, prior to washing and scanning. Data was extracted from the resulting images using Agilentâs Feature Extraction Software (Agilent Technologies, Inc., Palo Alto, CA).
2008-06-18 | E-GEOD-4270 | biostudies-arrayexpress
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
2024-11-05 | GSE237737 | GEO
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
2024-11-05 | GSE237747 | GEO
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
2024-11-05 | GSE237743 | GEO
Project description:Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less-known. We found that an epigenetic and energetic agent, acetyl-L-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line (FSL) rats. After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not respond (nrFSL). RNAseq for the ventral dentate-gyrus (vDG), a mood-regulatory region, identified metabolic factors as key markers predisposing to depression (insulin receptors Insr, glucose transporters Glut-4 and Glut-12, the regulator of appetite Cartpt) and to LAC responsiveness (leptin receptors Lepr, metabotropic glutamate receptors-2 mGlu2, neuropeptide-Y NPY, and mineralocorticoid receptors MR). Furthermore, we found that stress-induced treatment-resistance in nrFSL shows a new gene profile, including the metabolic regulator factors Elovl7 and Cyb5r2 and the synaptic regulator NPAS4. Finally, while improving central energy regulation and exerting rapid antidepressant-like effects, LAC corrected a systemic hyperinsulinemia and hyperglycemia.tance in rFSL and failed to do that in nrFSL. These findings establish CNS energy regulation as factor to be considered for the development of better therapeutics. Agents, like LAC, which regulate metabolic factors and reduce glutamate overflow, could rapidly ameliorate depression and could also be considered for treatment of insulin-resistance in depressed subjects. The approach here serves as a model for identifying markers and underlying mechanisms of predisposition to diseases and treatment responsiveness that may be useful in translation to human behavior and psychopathology. Ventral dentate gyrus RNA from 3 biological replicates per group (vehicle-FRL, vehicle-FSL, LAC-treated not-responder FSL, LAC-treated responder FSL, all males) was used for library prep (TruSeq Stranded Total RNA with Ribo-Zero Human/Mouse/Rat) and sequenced on Illumina HiSeq2500 at the Genomic Core facility at The Rockefeller University. Each sample was provided with a unique adapter and all samples were put in the same pool and run in multiple lanes to control for lane effects with a sequencing depth of about 30M (100bp, single).
2016-07-01 | E-GEOD-83336 | biostudies-arrayexpress