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. Experiment Overall Design: Male Sprague-Dawley rats were given a single, oral, non-seizure inducing dose of either 3 or 18 mg/kg RDX in a gel capsule. Rats were euthanized at times 0, 4, 24, and 48 hours. RNA purified from brain cortex or liver was hybridized to Affymetrix rat 230.2 arrays.
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.
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.
Project description:A series of two color gene expression profiles obtained using Agilent 44K expression microarrays was used to examine sex-dependent and growth hormone-dependent differences in gene expression in rat liver. This series is comprised of pools of RNA prepared from untreated male and female rat liver, hypophysectomized (‘Hypox’) male and female rat liver, and from livers of Hypox male rats treated with either a single injection of growth hormone and then killed 30, 60, or 90 min later, or from livers of Hypox male rats treated with two growth hormone injections spaced 3 or 4 hr apart and killed 30 min after the second injection. The pools were paired to generate the following 6 direct microarray comparisons: 1) untreated male liver vs. untreated female liver; 2) Hypox male liver vs. untreated male liver; 3) Hypox female liver vs. untreated female liver; 4) Hypox male liver vs. Hypox female liver; 5) Hypox male liver + 1 growth hormone injection vs. Hypox male liver; and 6) Hypox male liver + 2 growth hormone injections vs. Hypox male liver. A comparison of untreated male liver and untreated female liver liver gene expression profiles showed that of the genes that showed significant expression differences in at least one of the 6 data sets, 25% were sex-specific. Moreover, sex specificity was lost for 88% of the male-specific genes and 94% of the female-specific genes following hypophysectomy. 25-31% of the sex-specific genes whose expression is altered by hypophysectomy responded to short-term growth hormone treatment in hypox male liver. 18-19% of the sex-specific genes whose expression decreased following hypophysectomy were up-regulated after either one or two growth hormone injections. Finally, growth hormone suppressed 24-36% of the sex-specific genes whose expression was up-regulated following hypophysectomy, indicating that growth hormone acts via both positive and negative regulatory mechanisms to establish and maintain the sex specificity of liver gene expression. For full details, see V. Wauthier and D.J. Waxman, Molecular Endocrinology (2008)
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.
Project description:Formaldehyde (HCHO) is the simplest form of aldehyde and it is naturally present in a wide range of resources. In spite of its cosmopolitan presence, formaldehyde can have deleterious health effects at higher concentrations like leukemia. However, most of the studies carried out so far have focused on the effect of formaldehyde exposure through inhalation and not much has been studied on the its exposure through food. In this context, the present study was carried out to investigate the effect of formaldehyde exposure through drinking water on the liver proteome of rat which would not only be helpful in assessing the impact of formaldehyde on health of organisms but also would be helpful in understanding the mechanism of detoxification.
Project description:We used RNA-seq to identify gene expression changes in C. elegans after 1 hr, 4 hr, 12 hr and 24 hr of exposure to Myzocytiopsis humicola extract; and after 12 hr, 24 hr and 48 hr of infection with Myzocytiopsis humicola
Project description:d-serine is naturally present throughout the human body. It is also used as add-on therapy for treatment-refractory schizophrenia. d-Serine interacts with the strychnine-insensitive glycine binding site of NMDA receptor, and this interaction could lead to potentially toxic activity (i.e., excitotoxicity) in brain tissue. The transcriptomic changes that occur in the brain after d-serine exposure have not been fully explored. Affymetrix microarray technology was used to determine differential gene expression resulting from D-Serine exposure. Keywords: Dose course Male Fisher 344 rats aged 11-12 weeks were treated with various doses (0, 5, 20, 50, 200 and 500 mg/kg) of d-serine and terminally sacrificed 96 hours post-exposure. An approximate 30mg-section of the forebrain was processed for total RNA isolation.