Effect of prenatal exposure to nicotine on kidney structure and gene expression in rats
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ABSTRACT: Here, we investigated whether prenatal exposure to nicotine alters kidney glomerular mass and genome-wide gene expression profiles in two genetically distant strains of rats, namely spontaneously hypertensive rats (SHR) and Brown Norway (BN) rats. Nicotine or saline were administered to BN and SHR dams via osmotic pumps throughout gestation. Kidneys from 9-week-old male offspring were studied. Equal amounts of RNA from individual animals were pooled within each of the four experimental groups SHR (nicotine: n=13; saline: n=12) and BN (nicotine: n=12; saline: n=12) and hybridized with the Rat RAE-230a GeneChip (Affymetrix).
Project description:Here, we investigated whether prenatal exposure to nicotine alters kidney glomerular mass and genome-wide gene expression profiles in two genetically distant strains of rats, namely spontaneously hypertensive rats (SHR) and Brown Norway (BN) rats. Nicotine or saline were administered to BN and SHR dams via osmotic pumps throughout gestation. Kidneys from 9-week-old male offspring were studied.
Project description:We compared tissue Na+ storage in salt sensitive spontaneously hypertensive rats (SHR) versus salt resistant normotensive Brown Norway (BN) rats after salt loading (10 days drinking 1% NaCl solution), the SHR showed significant parallel increase in osmotically inactive Na+ storage in the skin while no significant changes in skin electrolyte concentrations were observed in BN rats. SHR rats after salt treatment exhibited a nonsignificant decrease in skin blood capillary number (rarefaction) while BN rats showed significantly increased skin blood capillary density. Analysis of dermal gene expression profiles in BN rats after salt treatment showed significant up-regulation of genes involved in angiogenesis and proliferation of endothelial cells contrary to the SHR.
Project description:ADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6.The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR.
Project description:We used Nimblegen HD aCGH to detect copy-number variants between genomes of BN and SHR rats Comparison of single BN against single SHR individual in a dye-swap experiment
Project description:The development of hypertension may be highly influenced by the use of nicotine especially in genetically susceptible subjects. In this study the effects of nicotine on gene expression of cultured cells from the brainstem of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated using whole genome microarray platforms. It was described for the first time that nicotine may act differentially on the gene expression profile of SHR and WKY. The influence of strain was present in 348 genes that were differentially expressed in SHR as compared to WKY brainstem cells independently of the nicotine treatment. 176 genes had their expression altered in both strains after nicotine exposure. Interaction between nicotine treatment and the strain was observed for the expression of 269 genes which participate of cellular pathways related to neurotrabnsmitter secretion, intracellular trafficking and cell communication. In conclusion, this study leaves a list of genes whose expression shall be better studied since they are good candidates to the phenotypic differentiation between SHR and WKY, including hypertension as well as demonstrated that alterations in the systems of intracellular trafficking and neurotransmission may be relevant to the development of hypertension.
Project description:Four male SHR/Ola, BN and SHR-18 rats were fed a normal diet and sacrificed at 9 weeks of age. Four male SHR/Ola and SHR-18 rats at 8 weeks of age were fed 1% NaCl for one week and then sacrificed. Kidneys were removed and frozen in liquid nitrogen for all 20 animals. Total RNA was isolated, labelled cRNA was generated and hybridised to Affymetrix Rat RG-U34ABC arrays.
Project description:Gene expression data was generated in BN and SHR rats to correlate gene expression differences with CpG methylation differences detected between the strains by whole-genome bisulfite sequencing.
Project description:The rat models of colorectal cancer (CRC), such as the azoxymethane (AOM) cancer-inducing model, are important tools for researching cancer initiation pathways. However, there is limited understanding of the expression pathways of underlying normal rat colonic epithelium and how this relates to human colonic epithelium. The aim of this study was to study the acute effects of AOM on the gene and pathway expression of the rat's colonic epithelium, whilst contrasting the background normal global expression patterns along the length of the rat as compared to the normal human colonic epithelium. The study used microarrays to investigate global gene expression of the colonic epithelium from proximal and distal sections of AOM- and saline (normal)-treated Sprague Dawley rats. Rat gene and pathway expression patterns were then compared in-silico with human microarray data (see GSE9254 for files) from normal tissue samples originating from proximal and distal regions of the colon.