Gene expression in mice brain after ciguatoxin exposure
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE20949 | GEO | 2010/06/01
SECONDARY ACCESSION(S): PRJNA124433
REPOSITORIES: GEO
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Project description:This study characterizes the global transcriptional response in mouse brain to a symptomatic dose (0.26 ng/g) of the highly toxic Pacific ciguatoxin P-CTX-1 at 1, 4 and 24 hrs using whole genome microarrays Two-condition experiment, ciguatoxin treated vs vehicle treated mice. 9 Biological replicates: 9 control replicates, pooled into 3 control time points.
2010-06-01 | E-GEOD-20949 | biostudies-arrayexpress
Project description:Ciguatoxins (CTX) are polyether neurotoxins responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post exposure 2.4% of features on a 44K whole genome array were differentially expressed (p � 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Early gene expression was likely influenced prominently by an acute 4 °C decline in core body temperature by 1 h, which resolved by 8 h following exposure. Cytochrome P450s were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial down-regulation at 1 h but were quickly and strongly up-regulated at 4 and 24 h post exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. Experiment Overall Design: Individual C57/BL6 mice (n=3) exposed to 0.26 ng/g P-CTX-1 ip for 1, 4, or 24 h were compared to pooled time-matched controls (n=3). The triplicate arrays at each time point included a dye swap.
2008-06-20 | E-GEOD-10768 | biostudies-arrayexpress
Project description:Ciguatoxins (CTX) are polyether neurotoxins responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Early gene expression was likely influenced prominently by an acute 4 °C decline in core body temperature by 1 h, which resolved by 8 h following exposure. Cytochrome P450s were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial down-regulation at 1 h but were quickly and strongly up-regulated at 4 and 24 h post exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. Keywords: biotoxin, time course
2008-05-08 | GSE10768 | GEO
Project description:Peripheral blood mononuclear cells (PBMCs) were isolated using Histpaque-1077 (Sigma-Aldrich, Belgium) from 10 healthy donors (5 males, 5 females, aged 23-50). Isolated cells were resuspended at a density of 10^6 cells/ml and allowed to equilibrate to culture conditions at 37°C in a humidified 5% CO2 atmosphere. PBMCs were then exposed to 0.0 (sham), 0.1 or 1.0 Gy of X-rays (250 keV - 1 mA, 1 mm Cu) at a dose rate of 0.26 Gy/min. After irradiation, cells were incubated at 37°C in a humidified 5% CO2 atmosphere for 8 h before RNA extraction using the AllPrep DNA/RNA/protein Mini kit (Qiagen). Two weeks later, the experiment was repeated using fresh PBMCs from the same donors, resulting in a total of 60 RNA samples. Total RNA (250 ng) was used for hybridisation to GeneChip Human Gene 1.0 ST arrays (Affymetrix) using the WT expression kit (Ambion), GeneChip Terminal labeling kit (Affymetrix) and the GeneChip Hybridization, Wash and Stain kit (Affymetrix) according to the manufacturer's recommendations.
2016-01-14 | E-MTAB-3463 | biostudies-arrayexpress
Project description:Domoic acid (DA) is a naturally produced neurotoxin synthesized by the marine diatom genus Pseudo-nitzschia. DA accumulates in filter-feeders such as shellfish, and can produce severe neurotoxicity when contaminated seafood is ingested. DA poisoning is a significant public health concern, and though seafood regulations have effectively minimized the human risk of severe acute poisoning, the effects of exposure at asymptomatic levels are poorly understood. The objective of this study was to determine the effects of exposure to symptomatic and asymptomatic doses of DA on gene expression patterns in the zebrafish brain. We exposed adult zebrafish to either a symptomatic (1.1 ± 0.2 μg /g) or an asymptomatic (0.31 ± 0.03 µg DA/g fish) dose of DA by intracelomic injection and sampled at 24, 48 and 168 h post-injection. Transcriptional profiling was done using Agilent and Affymetrix microarrays. Our analysis revealed distinct, non-overlapping changes in gene expression between the two doses. We found that the majority of transcriptional changes were observed at 24 hours post-injection with both doses. In response to symptomatic dose exposure, we observed 328, 5, and 1 genes were differentially expressed at 24, 48 and 168 hours post-injection, respectively. In contrast, 136, 12, and 28 genes were differentially expressed in the asymptomatic dose at the same time points. Pathway analysis revealed symptomatic DA exposure affected genes associated with pathways including cell adhesion, inflammation, and amyloid proteins. Among the pathways enriched among genes differentially expressed with asymptomatic exposure were circadian rhythms and endocrine signaling. Overall, these results suggest that transcriptional responses are specific to the DA dose and that asymptomatic exposure can cause long-term changes. Many of the differentially expressed genes are important players in neuronal, neuroimmune and neuroendocrine function. Further studies are needed to characterize the potential downstream neurobehavioral impacts of DA exposure.
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Project description:To identify the activity-induced gene expression programs in inhibitory and excitatory neurons, we analyzed RNA extracted from cultured E14 mouse MGE- and CTX-derived neurons (DIV 10) after these cultures were membrane-depolarized for 0, 1 and 6 hrs with 55mM extracellular KCl. To identify the gene programs regulated in these cells by the activity-induced early-response transcription factor Npas4, we repeated the same experiment in the MGE- and CTX-cultures lacking Npas4 (Npas4-KO).
2015-06-04 | GSE55588 | GEO
Project description:Development of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice receiving non-toxic and toxic LNA gapmers after a single and repeat administration. To understand the mechanism of LNA gapmer-induced heptotoxicity in mice, we investigated the transcription profiles of liver RNA isolated from mice receiving non-toxic sequence (NTS-1), toxic sequence (TS-2), or severely toxic sequence (HTS-3) of LNA gapmers at 25 mg/kg (dose volume of 10 mL/kg) at 8, 16, or 72 hrs after a single administration (by subcutaneous injection ) using microarray analysis. We also investigated the transcription profiles of liver RNA isolated from mice receiving non-toxic sequence (NTS-1) or toxic sequence (TS-2) of LNA gapmers at 25 mg/kg (dose volume of 10 mL/kg) at 2 weeks after repeated administration (by subcutaneous injection ) using microarray analysis.
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Project description:This study investigates host-specific gene expression of the Pacific salmon lice, Lepeophtheirus salmonis oncorhynchii, while parasitizing a resistant host (Coho salmon), two susceptible hosts (Atlantic salmon, Sockeye salmon), and a population with-held hosts (starved), over 48 hrs.
2017-01-25 | GSE80220 | GEO
Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.
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