Transcription profiling of mouse cerebral cortex using two model strains (C57BL/6 and ApoE(-/-) on the C57BL background) upon episode hypoxia treatment
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ABSTRACT: Study the gene expression variation at cerebral cortex using two mouse model strains (C57BL/6 and ApoE(-/-) on the C57BL background) upon episode hypoxia treatment
Project description:This study examines the relationship between sleep apnea and glucose metabolism. Physiological studies have demonstrated that 5 days of exposure to intermittent hypoxia (similar to what occurs with sleep apnea) leads to significant improvements in glucose tolerance. Therefore, this study investigates the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action.
Project description:Changes in gravitational force such as that experienced by astronauts during space flight induce a redistribution of fluids from the caudad to the cephalad portion of the body together with an elimination of normal head-to-foot hydrostatic pressure gradients. To assess brain gene profile changes associated with microgravity and fluid shift, a large-scale analysis of mRNA expression levels was performed in the brains of 2 weeks control and hindlimb-unloaded (HU) mice using cDNA microarrays. Although to different extent, all functional categories displayed significantly regulated genes indicating that considerable transcriptomic alterations are induced by HU. Interestingly, the TIC class (transport of small molecules and ions into the cells) had the highest percentage of up-regulated genes, while the most down-regulated genes were those of the JAE class (Cell junction, Adhesion, Extracellular Matrix). TIC genes comprised 16% of those whose expression was altered, including sodium channel, nonvoltage-gated 1 beta (Scnn1b), glutamate receptor (Grin1), voltage-dependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by GeneMAPP revealed several altered protein classes and functional pathways such as blood coagulation and immune response, learning and memory, ion channels and cell junction. In particular, data indicate that HU causes an alteration in hemostasis which resolves in a shift toward a more hyper-coagulative state with an increased risk of venous thrombosis. Furthermore, HU treatment seems to impact on key steps of synaptic plasticity and learning processes. We used brains of four control (C1, C2, C3, C4) and four tail-suspended hindlimb-unloaded (E1, E2, E3, E4) mice to ensure statistical relevance of the study. 60 ug of total RNA extracted in TRIzol from each brain was reversed transcribed into labeled cDNAs using fluorescent Cy5 or Cy3-dUTP (Amersham Biosciences, NJ). Differently labeled cDNAs obtained from a pair of biological replicas were co-hybridized overnight at 50C with a microscope slide spotted with ~ 27,000 mouse cDNA sequences produced by the Microarray Core Facility of the Albert Einstein College of Medicine in the “multiple yellow” design (i.e.: C1C2, C3C4, E1E2, E3E4), described in Iacobas DA, Fan C, Iacobas S et al., Transcriptomic changes in developing kidney exposed to chronic hypoxia. Biochem Biophys Res Commun. 2006 349(1):329-38).
Project description:Ischemic heart disease continues to rank highly among cardiovascular diseases in the world. Myocardial reperfusion (R) is provided with an effective and rapid treatment, however it can lead to fatal results as well as ischemia (I). The goal of this study was to use proteomic analysis to assess the proteins and pathways that changed in H9C2 cardiomyocyte cells exposed to (I) and (R) for durations that represented acute and chronic conditions.
Project description:In this study we investigated whether there exists a genomic signature that can accurately predict the course of a respiratory syncytial virus (RSV) infection in hospitalized young infants. We used early blood microarray transcriptome profiles from 39 infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease.
Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention. A total of 14 samples were profiled for microbiome composition: 7 from non-sinusitis patients, and 7 from patients with clinically diagnosed chronic sinusitis.
Project description:We analyzed cerebral cortices (CTX) and midbrains (MB) from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. Samples from CTX and MB of 21 mice: 7 Naïve, 7 Air-2BC, and 7 CIE-2BC. One channel was used for the actual sample, the second channel was used fot Internal QC Reference.
Project description:Microarray experiments have generally focused on magnitude of gene expression changes in pathological conditions, thereby using the method as a high throughput screen to identify candidate marker genes and/or to validate phenotypic differences. We have used novel strategies to extract additional information from array studies, including expression variability and coordination, from which organizational principles of transcriptomes are emerging. We have reported that expression level, variability and coordination of numerous genes are regulated in brains of Gja1-/- mice with respect to wildtypes. Moreover, expression coordination with Gja1 in wildtypes largely predicted expression regulation in Gja1-/- tissues. We now report a remarkable overlap between regulations in Gja1-/- and Gjb1-/- brains, and that both differ markedly from those in Gja9-/- brain. Since in brain these three connexins are expressed in different cell types (Gja1 in astrocytes, and ependymal and vascular cells, Gjb1 in oligodendrocytes, and Gja9 in neurons and microglia), and because astrocytes and oligodendrocytes may form syncytia coupled by gap junction channels, these observations suggest the existence of distinct connexin-dependent panglial and neuronal transcriptomic networks. Such networks, where linkage partners are rearranged and strengths modified in brains of knockouts, may explain downstream and parallel 'ripples' of phenotypic change resulting from single gene alterations as the composition and interactions of transcription factor networks in the wildtype brain were identified and found to be altered disruption of Gja1 or Gjb1. The transcription factors also formed network hubs with genes from other functional categories, thus allowing regulation of one functional pathway through manipulation of another. Keywords: genetic modification The brain transcriptomes of Gja9(-/-) and Gja9(+/-) P10 mice were compared to that of P10 wildtype mouse using the "multiple yellow" design in which extracts of biological replicas of the same genotype were hybridized with six 27k AECOM mouse cDNA microarrays (4 biological replicas of each genotype). These data were further compared to previously reported data on brain of neonatal wildtype, Gja1(-/-), Gja1(+/-) and Gjb1(-/-) mice (four biological replicas per genotype, reference sample design).
Project description:Time-course gene expression profiles were obtained from lung tissues of the rats treated with room air, intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days using CodeLink microarrays. Using a systems biology approach, we observed that two different mechanisms are involved in the lung responses to IH and SH: IH leads to increased G-protein coupled signaling-, ion transport-, neuronal- and steroid hormone receptor activities; whereas SH causes increased blood vessel morphogenesis and immune responses. Our results provide insight into molecular mechanisms underlying IH and SH. Keywords: gene expression array-based, count rats were treated with intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days; rats treated with room air were used as controls; gene expression profiles were obtained from these rats
Project description:Gene expression and phenotypic consequences of laboratory housing in rats. Disease related-phenotypes and associated gene expressions of sedentary animals (living solely in a standard cage) were compared with animals that had access to twice-weekly one-hour physical activity in a large box (PA) and with those that had access to voluntary running wheel exercise (EX). Experiment Overall Design: The left ventricle of 16 month female Sprague-Dawley rats was used for RNA extraction and hybridization on Affymetrix GeneChip Rat Genome 230 2.0 Arrays. Twelve animals from each treatment group (SED, PA, and EX) were used for microarray analysis (4 animals pooled per GeneChip).
Project description:Smoking cigarettes is harmful to the cardiovascular system. Considerable attention has been paid to the reduced harm potential of alternative nicotine-containing inhalable products such as e-cigarettes. We investigated the effects of E-vapor aerosols or cigarette smoke (CS) on atherosclerosis progression, cardiovascular function, and molecular changes in the heart and aorta of female ApoE−/− mice. The mice were exposed to aerosols from three different E-vapor formulations: (1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine) or (3) test (base and flavor) or to CS from 3R4F reference cigarettes for up to 6 months. Concentrations of CS and base or test aerosols were matched at 35 µg nicotine/L. Exposure to CS, compared with sham-exposed fresh air controls, accelerated atherosclerotic plaque formation, while no such effect was seen for any of the three E-vapor aerosols. Molecular changes indicated disease mechanisms related to oxidative stress and inflammation in general, plus changes in calcium regulation, and altered cytoskeletal organization and microtubule dynamics in the left ventricle. While ejection fraction, fractional shortening, cardiac output, and isovolumic contraction time remained unchanged following E-vapor aerosols exposure, the nicotine-containing base and test aerosols caused an increase in isovolumic relaxation time similar to CS. A nicotine-related increase in pulse wave velocity and arterial stiffness was also observed, but it was significantly lower for base and test aerosols than for CS. These results demonstrate that in comparison with CS, E-vapor aerosols induce substantially lower biological responses associated with smoking-related cardiovascular diseases.