Similar Datasets
Project description:Microarray analysis in vessels from control rats (Wistar-Kyoto rats) and disease model rats (Hypertensive rats)
| PRJNA875064 | ENA
Project description:DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.) Keywords: strain differences, exposure differences
2008-06-23 | GSE9694 | GEO
Project description:Systemic hypertension has a profound impact on the renal vascular physiology. In order to elucidate the biological pathways and macromolecules deregulated by hypertension renal vessels were obtained by Laser Capture Microdissection (LCM) from Spontaneously Hypertensive Rats (SHR) and age-matched controls (20 weeks). Proteomic analysis was performed aiming to detect early molecular alterations associated with hypertension at the renal vessels before the onset of vascular damage. Proteomic analysis identified 688 proteins, of which 58 were differentially expressed (15 up-regulated and 43 down-regulated in SHR). Many of these proteins are involved in vascular tone regulation by modulating the activity of endothelial Nitric Oxide Synthase (eNOS) (e.g. Xaa-Pro aminopeptidase 1 (XPP1), N(G) N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), Dehydropteridine reductase (DHPR)) or in blood pressure control by regulating the renin-angiotensin system (e.g. Glutamyl aminopeptidase/Aminopeptidase A (AMPE), Aminopeptidase N (AMPN)). Moreover, pathway enrichment analysis revealed that the eNOS activation pathway is deregulated only in SHR. Our study demonstrates that hypertension causes early proteomic changes in the renal vessels of SHR. These changes are relevant to vascular tone regulation and consequently may be involved in the development of vascular damage and hypertensive nephrosclerosis. Therefore, the identified proteins could be considered as therapeutic targets.
2022-03-03 | PXD008792 | Pride
Project description:Hypertension is a multifactor disease that possibly involves alterations in gene expression in hypertensive relative to normotensive subjects that are largely unknown. In this study we used high-density oligoarrays to compare gene expression profiles in cultured neurons and glia from pons and medulla oblongata of newborn spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, a widely documented animal model of hypertension. We found 358 genes differentially expressed between SHR and WKY brainstem cells that preferentially map to 24 metabolic/signaling pathways. Some of the pathways and regulated genes identified herein are obviously related to blood pressure regulation; however there are several genes differentially expressed in SHR not yet associated to hypertension or participating in blood pressure regulation. These constitute a rich resource for the identification and characterization of novel genes involved in hypertension development, or associated to phenotypical differences observed in SHR relative to WKI. In conclusion, this study describes for the first time the gene profiling pattern of brainstem cells from SHR and WKY rats, which opens up new possibilities and strategies of investigation and possible therapeutics to hypertension, as well as for the understanding of the brain contribution in this pathology. Keywords: Gene expression profiling of cultured cells from brainstem of spontaneously hypertensive and normotensive Wistar Kyoto rats
2008-12-31 | GSE10366 | GEO
Project description:Activation of autonomic neural pathways by chronic hypertensive stimuli plays a significant role in pathogenesis of hypertension. Here, we proposed that even a single acute hypertensive stimulus will activate neural and immune pathways that may be important in initiation of memory imprinting seen in chronic hypertension. We investigated the effects of acute angiotensin II (Ang II) administration on blood pressure, neural activation in cardioregulatory brain regions, and central and systemic immune responses, at 1 and 24 h post-injection. Administration of a single bolus intra-peritoneal (I.P.) injection of Ang II (36 μg/kg) resulted in a transient increase in the mean arterial pressure (MAP) (by 22 ± 4 mmHg vs saline), which returned to baseline within 1 h. However, in contrast to MAP, neuronal activity, as measured by manganese-enhanced magnetic resonance (MEMRI), remained elevated in several cardioregulatory brain regions over 24 h. The increase was predominant in autonomic regions, such as the subfornical organ (SFO; ~20%), paraventricular nucleus of the hypothalamus (PVN; ~20%) and rostral ventrolateral medulla (RVLM; ~900%), among others. Similarly, systemic and central immune responses, as evidenced by circulating levels of CD4+/IL17+ T cells, and increased IL17 levels and activation of microglia in the PVN, respectively, remained elevated at 24 h following Ang II challenge. Elevated Fos expression in the PVN was also present at 24 h (by 73 ± 11%) following Ang II compared to control saline injections, confirming persistent activation of PVN. Thus, even a single Ang II hypertensive stimulus will initiate changes in neuronal and immune cells that play a role in the developing hypertensive phenotype.
| S-EPMC5583219 | biostudies-literature
Project description:Altered gastric accommodation and intestinal morphology suggest impaired gastrointestinal (GI) transit may occur in the Wistar-Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague-Dawley (SD) rats under basal conditions and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor gastric emptying (4 h), small intestine (SI) transit (9 h), and large intestine transit (12 h). Plasma extracts were analyzed by lipid and hydrophilic interaction liquid chromatography (HILIC) and liquid chromatography-mass spectrometry (LC-MS). Cecal microbial composition was determined by Illumina MiSeq 16S rRNA amplicon sequencing and analysis using the QIIME pipeline. Stomach retention of beads was 77% for WKY compared with 35% for SD rats. GI transit was decreased by 34% (9 h) and 21% (12 h) in WKY compared with SD rats. Excluding stomach retention, transiting beads moved 29% further along the SI over 4-9 h for WKY compared with SD rats. Cecal Ruminococcus, Roseburia, and unclassified Lachnospiraceae genera were less abundant in WKY rats, whereas the minor taxa Dorea, Turicibacter, and Lactobacillus were higher. Diglycerides, triglycerides, phosphatidyl-ethanolamines, and phosphatidylserine were lower in WKY rats, whereas cholesterol esters and taurocholic acids were higher. The unexpected WKY rat phenotype of delayed gastric emptying, yet rapid SI transit, was associated with altered lipid and metabolite profiles. The delayed gastric emptying of the WKY phenotype suggests this rat strain may be useful as a model for gastroparesis.NEW & NOTEWORTHY This study reveals that the stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis and rapid small intestine transit, together with metabolic changes consistent with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats. This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model for gastroparesis.
| S-EPMC5538835 | biostudies-literature
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.
2009-09-16 | GSE13311 | GEO
Project description:There is an ongoing debate about the value of animal research in psychiatry with valid lines of reasoning stating the limits of individual animal models compared to human psychiatric illnesses. Human depression is not a homogenous disorder; therefore, one cannot expect a single animal model to reflect depression heterogeneity. This limited review presents arguments that the Wistar Kyoto (WKY) rats show intrinsic depression traits. The phenotypes of WKY do not completely mirror those of human depression but clearly indicate characteristics that are common with it. WKYs present despair- like behavior, passive coping with stress, comorbid anxiety, and enhanced drug use compared to other routinely used inbred or outbred strains of rats. The commonly used tests identifying these phenotypes reflect exploratory, escape-oriented, and withdrawal-like behaviors. The WKYs consistently choose withdrawal or avoidance in novel environments and freezing behaviors in response to a challenge in these tests. The physiological response to a stressful environment is exaggerated in WKYs. Selective breeding generated two WKY substrains that are nearly isogenic but show clear behavioral differences, including that of depression-like behavior. WKY and its substrains may share characteristics of subgroups of depressed individuals with social withdrawal, low energy, weight loss, sleep disturbances, and specific cognitive dysfunction. The genomes of the WKY and WKY substrains contain variations that impact the function of many genes identified in recent human genetic studies of depression. Thus, these strains of rats share characteristics of human depression at both phenotypic and genetic levels, making them a model of depression traits.
| S-EPMC10514523 | biostudies-literature
Project description:The spontaneously hypertensive rat (SHR) has been widely used as a model for studies of hypertension and attention deficit/hyperactivity disorder. The inbred Wistar-Kyoto (WKY) rat, derived from the same ancestral outbred Wistar rat as the SHR, are normotensive and have been used as the closest genetic control for the SHR, although the WKY has also been used as a model for depression. Notably, however, substantial behavioral and genetic differences among the WKY substrains, usually from the different vendors and breeders, have been observed. These differences have often been overlooked in prior studies, leading to inconsistent and even contradictory findings. The complicated breeding history of the SHR and WKY rats and the lack of a comprehensive understanding of the genetic background of different commercial substrains make the selection of control rats a daunting task, even for researchers who are mindful of their genetic heterogeneity. In this study, we examined the genetic relationship of 16 commonly used WKY and SHR rat substrains using genome-wide SNP genotyping data. Our results confirmed a large genetic divergence and complex relationships among the SHR and WKY substrains. This understanding, although incomplete without the genome sequence, provides useful guidance in selecting substrains and helps to interpret previous reports when the source of the animals was known. Moreover, we found two closely related, yet distinct WKY substrains that may provide novel opportunities in modeling psychiatric disorders.
| S-EPMC3727021 | biostudies-literature
Project description:Acute acrolein inhalation in male rats resulted in multi-tissue transcriptomic alterations that were observed through Illumina mRNA sequencing. Specifically, site-specific respiratory expression profile differences were noted between air- and acrolein-exposed groups. Nasal epithelial tissue demonstrated 452 differentially expressed genes (DEGs) (310 up-regulated and 142 down-regulated)and lung tissue demonstrated 95 DEGs (80 up-regulated and 15 down-regulated). Notable transcriptomic alterations were also observed in liver tissue of acrolein-exposed rats, with 1699 identified DEGs (788 up-regulated and 911 down-regulated). A variety of mRNA expression profile differences resulting from acute acrolein inhalation was observed in other peripheral tissues, including adipose, muscle, adrenals, hippocamus, and hypothalamus. Gene changes were largely representative of oxidative and inflammatory response in the nose, as well as xenobiotic metabolism changes in the lung. Liver changes, which were most numerous, included alterated metabolic signaling (Sirtuin and FXR signaling), as well as alterated oxidoreductive, GPCR, and glucocorticoid pathways. Together, these data demonstrate acrolein, a well-characterized respiratory irritant, induces systemic neuroendocrine immunological and metabolic stress.
2023-11-16 | GSE247698 | GEO