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Investigating RDX neurotoxicity in rat brain using gene expression analysis and transcriptional network modeling

ABSTRACT: ABSTRACT: The central nervous system is remarkably plastic in its ability to recover from trauma. We examined recovery from hexahydro-1,3,5-trinitrotriazine (RDX) induced seizures in rat through changes in transcriptional networks. Transcriptional networks from time series experiments provide a good basis for organizing and studying the dynamic behavior of biological processes. The goal of this work was to identify networks affected by chemical exposure and track changes in these networks as animals recover. We examined brain microarray data from rats exposed to 0, 1.2, 12, 24, and 47 mg RDX/kg body weight at different time points after exposure (24hr, 48hr, 7d, 14d, 28d and 90d). RESULTS A credible transcriptional network was constructed from the gene expression microarray data, which predicts the role of some key genes such as heat shock proteins, neuropeptide Y, thyrotropin-releasing hormones, growth factors, and ion channels in neurotransmission and neuroprotective mechanisms. Examination of the dynamic changes in expression within this network over time provided insight into CNS protective mechanisms from traumas.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE27042 | GEO | 2011/05/31

SECONDARY ACCESSION(S): PRJNA137645

REPOSITORIES: GEO

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Investigating RDX neurotoxicity in rat brain using gene expression analysis and transcriptional network modeling

Project description:ABSTRACT: The central nervous system is remarkably plastic in its ability to recover from trauma. We examined recovery from hexahydro-1,3,5-trinitrotriazine (RDX) induced seizures in rat through changes in transcriptional networks. Transcriptional networks from time series experiments provide a good basis for organizing and studying the dynamic behavior of biological processes. The goal of this work was to identify networks affected by chemical exposure and track changes in these networks as animals recover. We examined brain microarray data from rats exposed to 0, 1.2, 12, 24, and 47 mg RDX/kg body weight at different time points after exposure (24hr, 48hr, 7d, 14d, 28d and 90d). RESULTS A credible transcriptional network was constructed from the gene expression microarray data, which predicts the role of some key genes such as heat shock proteins, neuropeptide Y, thyrotropin-releasing hormones, growth factors, and ion channels in neurotransmission and neuroprotective mechanisms. Examination of the dynamic changes in expression within this network over time provided insight into CNS protective mechanisms from traumas. Single RDX Exposure with Various Time Points, Brain Tissue Investigation: Sprague-Dawley female rats were exposed to a single oral gavage of one of four concentrations of RDX or vehicle control with sampling periods of 24h, 48h, 7d, 14d, 28d, or 90d. Brain tissue was investigated for differential expression in response to RDX exposure and provide insight into CNS protective mechanisms associated with RDX exposure.

2011-05-31 | E-GEOD-27042 | biostudies-arrayexpress

Rat exposure to RDX (3mg/kg or 18mg/kg; 0, 4, 24, 48 hr)

Project description:RDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur either occupationally or through ordnance that lays unexploded on training ranges. The toxicology of RDX is dominated by acute tonic-clonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Sub-chronic studies have revealed few other toxic effects. The objective of this study was to examine the effect of a single oral dose of RDX on global gene expression in the mammalian brain and liver, using a rodent model. Keywords: time course, dose response

2009-03-13 | GSE12196 | GEO

Profiling differentially expressed earthworm genes in response to TNT, RDX, or TNT+RDX exposure.

Project description:To understand molecular mechanisms of the joint effects of 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), both widely used ordnance compounds, we constructed a microarray consisting of 4,032 cDNA isolated from the earthworm Eisenia fetida using the suppressive subtractive hybridization technique. Worms were exposed to TNT-, RDX-, or TNT+RDX-spiked soil for 28 days (TNT 50 mg/kg, RDX 30 mg/kg). Keywords: Combined toxicity of TNT and RDX to earthworm (Eisenia fetida)

2008-08-28 | GSE8909 | GEO

Shewanella sediminis HAW-EB3

Project description:Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)-degrading bacterium

| PRJNA18789 | ENA

Expression analysis of Gordonia sp. KTR9 upon exposure to RDX and Nitrogen limitation

2013-02-06 | GSE42340 | GEO

Profiling differentially expressed earthworm genes in response to TNT, RDX, or TNT+RDX exposure.

2008-08-28 | E-GEOD-8909 | biostudies-arrayexpress

Expression analysis of Gordonia sp. KTR9 upon exposure to RDX and Nitrogen limitation

Project description:Investigation of gene expression level changes in Gordonia sp. KTR9 upon exposure to RDX and Nitrogen Limitation, compared to controls with no RDX. The Gordonia sp. KTR9 strain used in this study has been previously described by Thompson KT, Crocker FH, Fredrickson HL.2005. Mineralization of the cyclic nitramine explosive hexahydro-1,3,5-trinitro-1,3,5-triazine by Gordonia and Williamsia spp. Appl Environ Microbiol. 2005 Dec;71(12):8265-72. A 12 x 135K array study using total RNA recovered from triplicate cultures of KTR9 exposed to RDX, triplicate cultures of KTR9 exposed to RDX and high nitrogen conditions, triplicate cultures of KTR9 exposed to low nitrogen, and triplicate cultures of controls exposed to high nitrogen.

2013-02-06 | E-GEOD-42340 | biostudies-arrayexpress

Transcription profiling of rat liver or brain cortex exposured to the explosive rexahydro-1,3,5-trinitro-1,3,5-triazine - RDX (3mg/kg or 18mg/kg; 0, 4, 24, 48 hr)

2009-03-21 | E-GEOD-12196 | biostudies-arrayexpress

Neurotoxicogenomic investigations to assess mechanisms of action of the munitions constituents RDX and 2,6-DNT in Northern bobwhite (Colinus virginianus) (part 1 of 10)

Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (≤ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20× more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms.

2011-11-22 | GSE33888 | GEO

Neurotoxicogenomic investigations to assess mechanisms of action of the munitions constituents RDX and 2,6-DNT in Northern bobwhite (Colinus virginianus) (part 2 of 10)

2011-11-22 | GSE33893 | GEO

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