Expression data from adult mouse Nucleus Accumbens following prenatal infection
ABSTRACT: Prenatal exposure to infectious or inflammatory insults can increase the risk of neuropsychiatric disorders with neurodevelopmental components, including schizophrenia and autism. The molecular processes underlying this pathological association are only partially understood. Here, we implemented an unbiased genome-wide transcriptional profiling of the nucleus accumbens of mice exposed to prenatal infection on GD17 compared to control subjects in order to elucidate the long term molecular signature of late prenatal infection. We used microarray analysis to investigate the long lasting gene expression changes in a well-established mouse model that is based on maternal treatment with the viral mimic poly(I:C) during pregnancy C57BL/6 mice were treated with the synthetic viral mimetic poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on gestation day 17. Offspring were subjected to cognitive and behavioral testing in adulthood, and then whole genome gene expression analysis with Affymetrix Microarray and subsequent q-PCR validation were performed on the nucleus accumbens.
Project description:Prenatal exposure to infectious or inflammatory insults can increase the risk of neuropsychiatric disorders with neurodevelopmental components, including schizophrenia and autism. The molecular processes underlying this pathological association are only partially understood. Here, we implemented an unbiased genome-wide transcriptional profiling of the prefrontal cortex of mice exposed to prenatal infection on GD17 compared to control subjects in order to elucidate the long term molecular signature of late prenatal infection. We used microarray analysis to investigate the long lasting gene expression changes in a well-established mouse model that is based on maternal treatment with the viral mimic poly(I:C) during pregnancy C57BL/6 mice were treated with the synthetic viral mimetic poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on gestation day 17. Offspring were subjected to cognitive and behavioral testing in adulthood, and then whole genome gene expression analysis with Affymetrix Microarray and subsequent q-PCR validation were performed on the prefrontal Cortex.
Project description:Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. The metamorphosis of the fruit fly represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, the mechanisms that coordinate development and immune cell activity in the transition from larva to adult in Drosophila remain to elucidate. The steroid hormone ecdysone is known to act as a key coordinator of metamorphosis. This hormone activates a nuclear receptor, the Ecdysone Receptor (EcR), which acts as a heterodimer with its partner Ultraspiracle (USP). Together, they activate the transcription of primary response genes, which in turn activate the transcription of a battery of late response genes. We have revealed that regulation of macrophage-like cells (hemocytes) by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. We have shown that in response to ecdysone signalling, hemocytes rapidly up regulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential to hemocyte immune functions and survival after infection. To better understand the ecdysone regulation of hemocyte activities, we have performed gene expression analysis. In order to identify the genes which expression change at the onset of metamorphosis, we have sorted hemocytes from 3rd instar larvae and from young prepupae and compared their gene expression. Moreover, and in order to identify which genes are regulated by the ecdysone signalling, we have used individuals expressing a dominant negative form of the Ecdysone Receptor specifically in their hemocytes. We have sorted hemocytes from 3rd instar and young prepupae of this genotype to compare their gene expression to the gene expression in larvae and prepupae from the control individuals. Hemocytes were isolated by FACS from selected 3rd instar larvae (at the late feeding stage) and prepupae (from 1h to 2h after puparium formation - APF) corresponding to two different genotypes: individuals w;HmlDeltaGal4, UAS-GFP/+ that express GFP specifically in hemocytes (genotype control), and individuals w;HmlDeltaGal4; UAS-GFP/UAS-EcRB1DN W650A which hemocytes express an Ecdysone Receptor Dominant Negative construct in addition to the GFP (EcRDN). For each of the four conditions we performed three biological replicates.
Project description:Several recombinat viruses of porcine circovirus type 2 (PCV2),including P1, P2, ZJ-R, VL258, and VL264, have been found. The PK15 cells were transfected by the molecular clones of the abovementioned viruses, where specific sets of genes are up-regulated or down-regulated. We used microarrays to detail the global programme of gene expression and identified distinct functions of viruses or viral proteins. PK15 cells were selected at 12 hours post-transfection for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the gene expression patterns of PK15 cells transfected with different molecular clones of the viruses.
Project description:Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders. A microarray expression study was conducted comparing transcriptomic profiles of skin fibroblasts from SCZ patients and controls. Fibroblasts can be more advantageous to discover mental disorder aetiological mechanisms since they seem more similar to neurons and less affected by the environmental confounders. Transcriptomic profiles of human skin fibroblasts obtained from 20 schizophrenia patients were compared to 20 controls
Project description:To determine if there are differences in the gene expression profile of peripheral blood mononuclear cells in patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who responded to CPI-613 when compared to those patients who did not respond we generated gene expression profiles from four responding patients and compared them to four non-responders. None of the gene expression profiles have been previously published. Here we describe the origins and provide associated clinical annotations with the hope that other investigators will be able to utilize this data in their own research. Peripheral blood mononuclear cells were isolated from 4 patients (3 MDS, 1 AML) who responded to treatment with CPI-613 and four patients (all with AML) who did not respond. Total RNA was isolated and gene expression levels were profiled on the Affymetrix Gene Atlas U219 array strips.
Project description:The biological effects of TTR proteins in the vasculature remain unknown. We used microarrays to detail the modulation of gene expression on HUVECs by V30M TTR when compared to cells exposed to WT TTR. HUVECs (passage 7) were cultured in the presence of WT or V30M TTR at 4µM for 3 hours. RNA was extracted and hybridized on Affymetrix microarrays. We sought to obtain differentially expressed genes modulated by V30M TTR protein.
Project description:Gene expression profiling in dopaminergic brain structures of rats self-administering cocaine. Effect of histone deacetylase inhibition We have shown that injection of the HDAC inhibitor trichostatin A (TsA) to rats is sufficient to decrease their motivation to self-administer cocaine. The aim of the present study was to investigate alterations in gene expression patterns in the Anterior Cingulate Cortex and Nucleus Accumbens of rats self-administering cocaine and treated repeatedly with TsA, and compare them with rats taking only cocaine. We used Affymetrix microarrays to identify genes the expression of which was up-regulated or downregulated during this process. Drug self-administration was performed in dark operant chambers under a fixed-ratio 1 schedule of reinforcement that was carried out for 4 days during daily 2 h sessions. Each nosepoke into the active hole triggered the i.v. delivery of a 40 μl cocaine solution (0,3 mg/kg/injection) under the control of the computer. Rats were sacrificed 2 h after the 4th self-administration session; the anterior cingulate cortex and the nucleus accumbens were then dissected. Two treatments comparison
Project description:The SnRK1 protein kinase, the plant ortholog of mammalian AMPK and yeast Snf1, is activated by the energy depletion caused by adverse environmental conditions. Upon activation, SnRK1 triggers extensive transcriptional changes to restore homeostasis and promote stress tolerance and survival partly through the inhibition of anabolism and the activation of catabolism. Despite the identification of a few bZIP transcription factors as downstream effectors, the mechanisms underlying gene regulation, and in particular gene repression by SnRK1, remain mostly unknown. microRNAs (miRNAs) are 20-24nt RNAs that regulate gene expression post-transcriptionally by driving the cleavage and/or translation attenuation of complementary mRNA targets. In addition to the well-established role of miRNAs as regulators of plant development, mounting evidence implicates miRNAs in the response to environmental stress. Given the involvement of miRNAs in stress responses and the fact that some of the SnRK1-regulated genes are miRNA targets, we postulated that miRNAs drive part of the transcriptional reprogramming triggered by SnRK1 activation. To test this we have performed comparative analyses of the transcriptional response to energy deprivation between WT and dcl1-9, a mutant deficient in miRNA biogenesis. To assess the impact of miRNA deficiency on the starvation response we performed transcriptomics analyses of WT and dcl1-9 plants by subjecting leaves to 6h of light (control) or darkness (starvation)
Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-1α in colon, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-1α+/+, Hif-1αLSL/LSL mice. Background & Aims: The progression and growth of solid tumors leads to a state where tumors outgrow their capacity for efficient oxygenation and nutrient uptake and an increase in tumor hypoxia. Tumor hypoxic response is mediated by hypoxia-inducible factor (HIF)-1a and HIF-2a. These transcription factors regulate a battery of genes that are critical for tumor oxygenation, tumor metabolism, and cell proliferation and survival. Therefore, inhibitors of HIF have been sought for as anti-neoplastic agents in several different kinds of cancers. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1a is beneficial, and can reduce intestinal inflammation. The efficacy of pharmacological agents that chronically activate HIF-1a are decreased due to the tumorigenic potential of HIF. However, recent advance in understanding HIF signaling have identified mechanisms, which could allow for isoform specific activators. Activation of HIF-2a increases colon carcinogenesis and progression in mouse models. However, the role of chronic HIF-1a activation is unclear in the progression in colon cancer. The present data demonstrates that activation of HIF-1a in epithelial cells does not increase colon carcinogens or progression in two mouse models of colon cancer, and provides the proof of principle that HIF-1a activation maybe safe as therapies for inflammatory bowel disease. Global gene expression profiling in colon RNAs isolated from 6- to 8-week-old Hif-1α+/+ (n=5, Shah 019) and Hif-1αLSL/LSL (n=5, Shah 020).