Changes in miRNA expression in circulating whole blood resutling from exposure to neurotoxic doses of D-amphetamine
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PROVIDER: PRJNA476238 | ENA |
REPOSITORIES: ENA
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Project description:These experiments were designed to detect transcript (mRNA) changes in whole circulating blood in animals exposed to D-amphetamine under neurotoxic and non-neurotoxic conditions, or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The study objectives were: 1) to detect transcript changes in blood due to life-threatening hyperthermia produced by elevated environmental temperatures (39°C, produces no or minimal neurotoxicity); 2) detect transcripts that could serve as biomarkers specific for neurotoxic amphetamine exposures and not seen with environmentally-induced hyperthermia; and 3) determine the transcript changes related to the immune system in circulating blood produced by either non-neurotoxic or neurotoxic amphetamine exposures. Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood Five groups of animals were necessary to meet the study objectives. All groups were given 4 injections of either normal saline or amphetamine, and the injections were sequentially given with 2 h between each injection. Dosing started at 7:30 to 8:30 a.m. The groups are: 1) normothermic controls given normal saline in a 22.5°C environment; 2) controls given normal saline in a 16°C environment (also remained normothermic); 3) environmentally-induced hyperthermia given saline in a 39°C environment; 4) non-neurotoxic amphetamine given in a 16°C environment and 5) neurotoxic amphetamine group given amphetamine in a 22.5°C environment. Note the the saline controls (normothermic data) is contained in a separate but linked GEO file GSE62368
2015-12-08 | E-GEOD-64778 | biostudies-arrayexpress
Project description:These experiments were designed to detect transcript (mRNA) changes in whole circulating blood in animals exposed to D-amphetamine under neurotoxic and non-neurotoxic conditions, or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The study objectives were: 1) to detect transcript changes in blood due to life-threatening hyperthermia produced by elevated environmental temperatures (39°C, produces no or minimal neurotoxicity); 2) detect transcripts that could serve as biomarkers specific for neurotoxic amphetamine exposures and not seen with environmentally-induced hyperthermia; and 3) determine the transcript changes related to the immune system in circulating blood produced by either non-neurotoxic or neurotoxic amphetamine exposures. Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood
2015-12-08 | GSE64778 | GEO
Project description:These experiments were designed to compare the miRNA expression in whole circulating blood in animals exposed to D-amphetamine to the expression under control condition. This is the final set of RNA seq data to be generated by the experiments that have previously generated mRNA transcriptomes (GSE62368 and GSE64778). The study objectives were to detect miRNA changes in blood resulting from a neurotoxic exposure to amphetamine that may result from organ and tissue damage or immune function changes Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood
2018-12-18 | GSE115835 | GEO
Project description:These experiments were designed to produce the appropriate controls so that their cohort's transcript (mRNA) changes in whole circulating blood could be determined. The cohorts were exposed to D-amphetamine under a neurotoxic and non-neurotoxic condition or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The cohort data is in a separate, but linked, GEO file. Animals were given four doses of 1 ml/ kg of normal saline with two hours in between each dose. The animals body temperature was determined every 1 h and the rats were sacrificed 3 h after the last saline injection. Animals were not given access to food or water during this period so that they were more suitable controls for the amphetamine treatment groups
2015-12-08 | E-GEOD-62368 | biostudies-arrayexpress
Project description:These tissue were harvested to complement and extend the studies that generated GSE23093. They served 3 purposes; 1) identify genes important to choroid plexus function and compare them with those important for meninges and associated vasculature (MAV) function, 2) determine genes in the choroid plexus and sensitivity hyperthermia and amphetamine toxicity, 3) identify the important gene expression changes related to the immune system in MAV, choroid plexus and trunk' blood Gene mRNA expression patterns in choroid plexus and trunk blood were determined under control conditions as well as after (3 hr and 1day) exposure to either environmentally-induced hyperthermia or neurotoxic doses of amphetamine. This data was analyzed and compared to data from meninges and associated vasculature previously deposited in GEO. The data gathered under control conditions was used to further understand how the choroid plexus and meninges and associated vasculature might function to generate and regulate the cerebrospinal fluid. The expression patterns in the choroid plexus after environmentally-induced hyperthermia or neurotoxic doses of amphetamine was determine its damage and protective responses. The expression patterns after environmentally-induced hyperthermia or neurotoxic doses of amphetamine were compared among choroid plexus, meninges and associated vasculature and blood were analyzed to determine immune system responses.
2012-08-01 | E-GEOD-29733 | biostudies-arrayexpress
Project description:These experiments were designed to produce the appropriate controls so that their cohort's transcript (mRNA) changes in whole circulating blood could be determined. The cohorts were exposed to D-amphetamine under a neurotoxic and non-neurotoxic condition or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The cohort data is in a separate, but linked, GEO file.
2015-12-08 | GSE62368 | 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.
2009-07-06 | E-GEOD-12140 | biostudies-arrayexpress
Project description:Changes in transcript expression in circulating whole blood resulting from exposure to neurotoxic doses of D-amphetamine or Heat Stroke/Hyperthermia
| PRJNA271851 | ENA
Project description:Oligo array analysis with bioinformatics tools identified genes with very high expression levels in the meninges, arachnoid and pial membranes, and associated vasculature (MAV) as potentially important and unique to these tissues in rat. It was also determined whether these genes were more sensitive to expression changes after a neurotoxic exposure to amphetamine (AMPH). Gene expression in the vascular rich MAV was compared to the neuronal rich tissues of the striatum and parietal cortex. In controls, 850 genes differed by more than 5-fold when comparing the MAV to both striatum and parietal cortex. Genes specifically identified with the blood-brain barrier (BBB) were also expressed at high levels indicating they may help form tight junctions in MAV. Genes with 15-fold or greater expression in MAV compared to striatum or cortex are of potential uniqueness and importance to MAV function. Many of the identified genes are abundant in different types of epithelial tissue and function in binding, transport or metabolize ions and solute, and may help MAV regulate cerebrospinal fluid. Many others with high expressions are involved in immune system function possibly serving to facilitate lymphocyte and macrophage trafficking in vasculature and cerebrospinal fluid. Expression in the MAV has similarities to the choroid plexus indicating considerable overlap in functions. Genes in MAV with a higher expression (relative to brain) were affected in greater numbers than expected by EIH and AMPH (SIGNIFICANT?). Many expression increases evoked by AMPH and EIH in MAV relate to reactive oxidative stress and inflammation. However, AMPH induced more robust alterations in the expression of genes related to ion/solute transport, lipid metabolism, bacterial infection and damage than EIH. The BBB-related genes Sox18 and Cldn5 expression decreased more with AMPH than EIH, and Cldn 9 and Esam were increase only by AMPH. It is not known how these changes affect BBB function and integrity. Gene expression patterns in MAV were compared to two regions of brain (striatum and parietal cortex) to identify genes important to MAV function and determine whether their expressions were sensitive to a neurotoxic exposure to amphetamine.
2010-08-24 | E-GEOD-23093 | biostudies-arrayexpress
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
2009-07-06 | GSE12140 | GEO