Transcription profiling of mouse brain to identify age-related transcriptional changes and the effect of dietary supplementation of vitamin E
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ABSTRACT: We established the transcriptional profile of brain aging and examine the global effects of vitamin E supplementation on age-related alterations in expression in the aged mouse brain. Experiment Overall Design: Gene expression profiles were obtained from the neocortex tissues of 5-month-old controls, 30-month-old controls and 30-month old B6C3F1 mice with middle age-onset supplementation of alpha-tocopherol or a mixture of alpha and gamma-tocopherol (500mg/kg of each tocopherol).
Project description:This SuperSeries is composed of the following subset Series:; GSE8146: Age-related transcriptional changes and the effect of dietary supplementation of vitamin E in the mouse heart; GSE8150: Age-related transcriptional changes and the effect of dietary supplementation of vitamin E in the mouse brain Experiment Overall Design: Refer to individual Series
Project description:To investigate the global effects of vitamin E supplementation on heart aging, we used high-density oligonucleotide arrays to measure transcriptional alterations in 30-month-old B6C3F1 mice supplemented with α- and γ-tocopherol since middle age (15 months). Experiment Overall Design: Gene expression profiles were obtained from 5-month-old controls, 30-month-old controls and 30-month-old mice supplemented with α-tocopherol (1g/kg), or a mixture of α- and γ-tocopherol (500mg/kg of each tocopherol).
Project description:Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. Gene expression in cerebral cortex and cerebellum of mice were determined using Agilent chips. To ensure higher quality results in gene expression data, we conducted microarrays on 4 mice per group. Young mice were 2 months old and the other aged mice were 29 months old at the time of use. Data were standardized using global normalization and pro-cessed by R-program. An absolute fold change threshold of greater than 1.5 was required to be considered for further analyses. Expression values were in log2 scale.
Project description:A 30-day nutritional trial in broiler chickens (Ross 308) was conducted to investigate how specific forms of vitamin E (α- and γ-tocopherol) and their combination impact liver gene expression when oxidative susceptibility of the organism is induced by high n-3 polyunsaturated fatty acids (PUFA) intake. Thirty-six one-day-old male broilers were fed a diet enriched with 5 % linseed oil to induce oxidative susceptibility. Beside negative (N) and positive (P) control group, experimental groups were supplemented with either: 67 mg/kg RRR-α-tocopherol (A), 67 mg/kg RRR-γ-tocopherol (G) or with combination of 33.5 mg/kg of each tocopherol (S). Whole chicken genome microarray analysis was performed on liver RNA and selected differentially expressed genes were confirmed by qRT-PCR.
Project description:The developmental transition to motherhood requires gene expression changes that alter the brain to prepare and drive the female to perform maternal behaviors. Furthermore, it is expected that the many physiological changes accompanying pregnancy and postpartum stages will impact brain gene expression patterns. To understand how extensive these gene expression changes are, we examined the global transcriptional response broadly, by examining four different brain regions: hypothalamus, hippocampus, neocortex, and cerebellum. Further, to understand the time course of these changes we performed RNA-sequencing analyses on mRNA derived from virgin females, two pregnancy time points and three postpartum time points. We find that each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions, across the time points. Additionally, several genes previously implicated in underlying postpartum depression change expression. This study serves as a comprehensive atlas of gene expression changes in the maternal brain in the cerebellum, hippocampus, hypothalamus, and neocortex. At each of the time points analyzed, all four brain regions show extensive changes, suggesting that pregnancy, parturition, and postpartum maternal experience substantially impacts diverse brain regions. Libraries were prepared from three independent biological replicates, mRNA for each biological replicate was derived from a single mouse brain, with each mouse brain being used to collect all four brain regions.
Project description:The peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate glucose and lipid homeostasis. Activation of PPARs has been explored for the treatment of type 2 diabetes and dyslipidemia. LDT409 is a novel fatty acid like compound that has been shown to be a pan-active PPAR agonist. This data explores the changes in the liver proteome of mice treated with LDT409 while fed either a chow or high fat diet.
Project description:We report RNA-sequencing from ventral mid brain and striatum from paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease. We observed several differentially expressed genes upon pesticide exposure which we analyzed by pathway analysis. We examined 3 replicates each for ventral mid brain and striatum per pesticide for RNA-Seq
Project description:The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and analysis issues. We demonstrate the consistency of results within a platform across test sites as well as the high level of cross-platform concordance in terms of genes identified as differentially expressed. The MAQC study provides a rich resource that will help build consensus on the use of microarrays in research, clinical and regulatory settings. Manuscripts related to the MAQC project have been published in Nature Biotechnology, 24(9), September, 2006. More information about the MAQC project can be found at http://edkb.fda.gov/MAQC/.<br><br>Expression data from two distinct reference RNA samples (A and B) in four titration pools were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Sample A = Stratagene Universal Human Reference RNA (UHRR, Catalog #740000), Sample B = Ambion Human Brain Reference RNA (HBRR, Catalog #6050), Sample C = Samples A and B mixed at 75%:25% ratio (A:B); and Sample D = Samples A and B mixed at 25%:75% ratio (A:B). In general, each microarray platform was tested at three sites and each sample was tested in five replicates at each test site. Samples (hybridizations) were named according to the following convention: Platform_Testsite_SampleRelicate. For example, AFX_2_B1 represents the hybridization (array) from platform AFX processed by test site 2 for the first replicate of sample B. Assignment of platform code: ABI = Applied Biosystems (microarray); AFX = Affymetrix; AG1 = Agilent one-color; AGL = Agilent two-color; GEH = GE Healthcare; ILM = Illumina; NCI = NCI two-color (Operon oligos); EPP = Eppendorf; TAQ = TaqMan (Applied Biosystems); QGN = QuantiGene (Panomics); GEX = StaRT-PCR (Gene Express); H25K = TeleChem two-color; H25K1 = TeleChem one-color; BIO = CapitalBio two-color (Operon oligos); BIO1 = CapitalBio one-color (Operon oligos); OPN = Operon two-color (Operon oligos); NMC = Norwegian Microarray Consortium two-color (Operon oligos).
Project description:Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Caloric restricted mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed significantly fewer TUNEL-positive staining cells and fewer cleaved caspase-3-positive staining cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 28 proapoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR or staying lean can retard this process by suppressing apoptosis in the inner ear tissue. Experiment Overall Design: To examine the effects of aging, a comparison of cochlea tissues from YC (3 samples) and MC (3 samples) mice was conducted. To examine the effects of calorie restriction (CR), a comparison of cochleae from MC (3 samples) and CR (3 samples) mice was conducted. We examined age-related changes in gene expression in the cochlea and calorie restriction-induced changes in gene expression in the cochlea. We pooled four cochleae from two mice for one sample and used three samples per group (n = 3). Quality control measures were not used. No replicates were done. Dye swap was not used.
Project description:Interferon-alpha Kinoid (IFN-K) is a therapeutic vaccine composed of IFN-alpha2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients (see GSE39088). Here, we analyzed extended follow-up data from IFN-K-treated patients, in terms of persistence of neutralizing anti-IFN± Abs, gene expression profiling and safety. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNalpha Ab titers and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFN± blockade on the expression of B cell associated transcripts. Extended clinical (SLEDAI, BILAG, Physician Global Assessment) and biological (binding and neutralizing anti-IFNalpha Ab titers, C3 concentrations and anti double-stranded (ds)DNA Ab titers) follow-up data were collected in 6 IFN-K-treated patients. In these patients, whole blood samples were collected in PAXgene Blood RNA tubes (Qiagen) every 6 months after completion of the initial study. RNA was extracted from these samples, and was also re-extracted from baseline (month 0) and day 168 (month 6) PAXgene tubes stored at -80° from the same patients, and from 10 healthy volunteers.