Inter-Strain Differences in Default Mode Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat.
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SUBMITTER: Huang SM
PROVIDER: S-EPMC4761976 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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.) Experiment Overall Design: Two strains of rats (Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were exposed to either diesel exhaust particles or clean air. Four biological replicates were used for each strain/treatment exposure. Total number of chips equals 16.
2008-10-20 | E-GEOD-9694 | biostudies-arrayexpress
Project description:We measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
2007-11-01 | E-GEOD-1675 | biostudies-arrayexpress
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: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:Cardiac hypertrophy is recognized as an independent risk factor for cardiac failure. Efficient management of hypertensive heart disease requires identification of factors that can possibly mediate the transition from hypertrophy to failure. Resident cardiac stem cells have a prominent role in the maintenance of cardiac tissue homeostasis. Decline in the proportion of healthy cardiac stem cells (CSCs) can affect tissue regeneration. In pathological conditions, apart from natural aging, an adverse microenvironment can lead to decrease in efficiency of CSCs. A systematic analysis of cardiac stem cell characteristics in pathological conditions has not been reported so far. Therefore, this study was designed with the objective of examining the age associated variation in stem cell attributes of Spontaneously hypertensive rat (SHR) in comparison with normotensive Wistar rat. Spontaneously hypertensive rat was used as the experimental model since the cardiac remodeling resembles the clinical course of hypertensive heart disease. CSCs were isolated from atrial explants. Stem cell attributes were assessed in 1-week, 6, 12 and 18-month-old male SHR, in comparison with age matched Wistar rats. In 1-week-old pups, stem cell attributes of SHR and Wistar were comparable. Migration potential, proliferative capacity, TERT expression, telomerase activity and the proportion of c-kit+ cells decreased with age, both in SHR and Wistar. DNA damage and the proportion of senescent CSCs increased with age both in SHR and Wistar rats. Age associated increase was observed in the oxidative stress of stem cells, possibly mediated by the enhanced oxidative stress in the microenvironment. The changes were more pronounced in SHR, and as early as six months of age, there was significant decrease in efficiency of CSCs of SHR compared to Wistar. The density of healthy CSCs determined as a fraction of the differentiated cells was remarkably low in 18-month-old SHR. Age associated decrease in functionally efficient CSCs was therefore accelerated in SHR. Considering the vital role of CSCs in the maintenance of a healthy myocardium, decrease in functionally efficient CSCs can be a precipitating factor in pathological cardiac remodeling. Elevated ROS levels in CSCs of SHR lends scope for speculation that decrease in efficiency of CSCs is mediated by oxidative stress; and that modulation of the microenvironment by therapeutic interventions can restore a healthy stem cell population and facilitate maintenance of cardiac homeostasis and prevent cardiac decompensation.
| S-EPMC5726722 | 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 influence of hypertension and aging alone on brain structure has been described extensively. Our understanding of the interaction of hypertension with aging to brain morphology is still limited. We aimed to detect the synergistic effects of hypertension and aging on brain morphology and to describe the evolution patterns of cerebral atrophy from spatial and temporal perspectives. In 8 spontaneously hypertensive rats (SHRs) and 5 Wistar-Kyoto rats, high-resolution magnetic resonance imaging scans were longitudinally acquired at 10, 24, 52, and 80 weeks. We analyzed the tissue volumes of gray matter, white matter, cerebral spinal fluid, and total intracranial volume (TIV), and then evaluated gray matter volume in detail using voxel-based morphometry (VBM) and region of interest-based methods. There were interactive effects on hypertension and aging in tissue volumes of gray matter, white matter, and TIV, of which gray matter atrophy was most pronounced, especially in elderly SHRs. We identified the vulnerable gray matter volume with combined effects of hypertension and aging in the septal region, bilateral caudate putamen, hippocampus, primary somatosensory cortex, cerebellum, periaqueductal gray, right accumbens nucleus, and thalamus. We automatically extracted the septal region, anterior cingulate cortex, primary somatosensory cortex, caudate putamen, hippocampus, and accumbens nucleus and revealed an inverted-U trajectory of volume change in SHRs, with volume increase at the early phase and decline at the late phase. Hypertension interacts with aging to affect brain volume changes such as severe atrophy in elderly SHRs.
| S-EPMC8670306 | biostudies-literature
Project description:Abnormal default mode network (DMN) connectivity has been found in schizophrenia and other psychotic disorders. However, there are limited studies on early onset psychosis (EOP), and their results show lack of agreement. Here, we investigated within-network DMN connectivity in EOP compared to healthy controls (HC), and its relationship to clinical characteristics. A sample of 68 adolescent patients with EOP (mean age 16.53 ± 1.12 [SD] years, females 66%) and 95 HC (mean age 16.24 ± 1.50 [SD], females 60%) from two Scandinavian cohorts underwent resting state functional magnetic resonance imaging (rsfMRI). A group independent component analysis (ICA) was performed to identify the DMN across all participants. Dual regression was used to estimate spatial maps reflecting each participant's DMN network, which were compared between EOP and HC using voxel-wise general linear models and permutation-based analyses. Subgroup analyses were performed within the patient group, to explore associations between diagnostic subcategories and current use of psychotropic medication in relation to connectivity strength. The analysis revealed significantly reduced DMN connectivity in EOP compared to HC in the posterior cingulate cortex, precuneus, fusiform cortex, putamen, pallidum, amygdala, and insula. The subgroup analysis in the EOP group showed strongest deviations for affective psychosis, followed by other psychotic disorders and schizophrenia. There was no association between DMN connectivity strength and the current use of psychotropic medication. In conclusion, the findings demonstrate weaker DMN connectivity in adolescent patients with EOP compared to healthy peers, and differential effects across diagnostic subcategories, which may inform our understanding of underlying disease mechanisms in EOP.
| S-EPMC8662331 | biostudies-literature