Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Changes in transcript expression in circulating whole blood resulting from exposure to neurotoxic doses of D-amphetamine or Heat Stroke/Hyperthermia

ABSTRACT: 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 (39Â°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 22.5Â°C environment; 2) controls given normal saline in a 16Â°C environment (also remained normothermic); 3) environmentally-induced hyperthermia given saline in a 39Â°C environment; 4) non-neurotoxic amphetamine given in a 16Â°C environment and 5) neurotoxic amphetamine group given amphetamine in a 22.5Â°C environment. Note the the saline controls (normothermic data) is contained in a separate but linked GEO file GSE62368

ORGANISM(S): Rattus norvegicus

SUBMITTER: John Bowyer

PROVIDER: E-GEOD-64778 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.

Bowyer John F JF Tranter Karen M KM Hanig Joseph P JP Crabtree Nathaniel M NM Schleimer Robert P RP George Nysia I NI

PloS one 20150715 7

Methods were developed to evaluate the stability of rat whole blood expression obtained from RNA sequencing (RNA-seq) and assess changes in whole blood transcriptome profiles in experiments replicated over time. Expression was measured in globin-depleted RNA extracted from the whole blood of Sprague-Dawley rats, given either saline (control) or neurotoxic doses of amphetamine (AMPH). The experiment was repeated four times (paired control and AMPH groups) over a 2-year span. The transcriptome of ...[more]

PMID: 26177368

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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.

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Dataset Information

Changes in transcript expression in circulating whole blood resulting from exposure to neurotoxic doses of D-amphetamine or Heat Stroke/Hyperthermia

Publications

Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.

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