Physicians’ Health Study II
Ontology highlight
ABSTRACT:
DISEASE(S): Cardiovascular Disease,Prostatic Neoplasms,Cardiovascular Diseases,Eye Disease,Colorectal Cancer,Cognitive Dysfunction,Cognitive Decline,Colorectal Neoplasms,Prostate Cancer,Eye Diseases,Cancer
PROVIDER: 2024787 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Chondro/osteoblastic and cardiovascular-disease associated genes are modulated in human coronary artery smooth muscle cells that calcify in the presence of phosphate and vitamin D sterols. Looking at the effect of media conditions with and without Vitamin D, paracalcitriol (a vitamin D analog), or R568 (a calcimimetic) vs. dose and time on calcification of human coronary smooth muscle cells. Experiment Overall Design: CASMCs were exposed to differentiation medium [beta glycerophosphate (10 mM), ascorbic acid (50 mg/ml), and dexamethasone (10-9 M) with and without calcitriol or paricalcitol (10-8 M) for 7 days, and total RNA was examined by microarray.
2008-10-21 | E-GEOD-11917 | biostudies-arrayexpress
Project description:Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.
2014-09-23 | GSE61326 | GEO
Project description:Huntington's disease is a genetic disease caused by a single mutation. It is characterised by progressive movement, emotional and cognitive deficits. R6/2 transgenic mice carrying the Huntington's disease mutation have a progressive neurological phenotype, including deterioration in cognitive function. The mechanism underlying the cognitive deficits in R6/2 mice is unknown, but dysregulated gene expression, reduced neurotransmitter levels and abnormal synaptic function are present before the cognitive decline becomes pronounced. Our goal here was to ameliorate the cognitive phenotype in R6/2 mice using a combination drug therapy (tacrine, moclobemide and creatine) aimed boosting neurotransmitter levels in the brain. Treatment from 5 weeks of age prevented deterioration in two different cognitive tasks until at least 12 weeks. However, motor deterioration continued unabated. Microarray analysis of global gene expression revealed that many genes significantly up- or down-regulated in untreated R6/2 mice had returned towards normal levels after treatment. Thus dysregulated gene expression was reversed by the combination treatment in the R6/2 mice and probably underlies the observed improvements in cognitive function. Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated.
2007-12-13 | E-GEOD-857 | biostudies-arrayexpress
Project description:Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. Sixty, middle-aged male F344 rats were divided into three groups, each receiving for 5-6 months a different dietary amount of cholecalciferol (vitamin D3; VitD3). Purified AIN-93G (Harlan-Teklad) diet was modified to contain low, medium or high VitD3 (IU/kg diet): High = 10,000, Standard (Control) = 1000; Low = 100. Animal weight and amount of food consumed was recorded 2-3 times/week. Serum levels of 25-hydroxy vitamin D were determined using liquid chromatography/tandem mass spectrometry (ZRT Laboratory). Hippocampal RNA was isolated, quantified and checked for RNA integrity. One low VitD3 sample failed RNA quality control. Remaining RNA samples were applied to Affymetrix Rat Gene 1.0 ST arrays (one array/subject). Pre-statistical filtering removed poorly annotated probe sets, low intensity signals, and outlier values (>2SD of the group mean). Filtered data were analyzed by 1-way ANOVA to identify significant differences and the False Discovery Rate (FDR) procedure was used to estimate the error of multiple testing. FDR was compared at 0.31 and 0.17. Significant genes were assigned to one of four idealized expression patterns using Pearson’s test and separated by the sign of their correlation; relative gene expression values are provided on the log-2 scale. Functional categorization for significant genes was determined using DAVID bioinformatic tools. Please note that 'Marked' and 'Unmarked' (in the sample titles) refers to whether the rat had a mark on its tail. The rats were pair-housed and this is how two rats in one cage were distinguished.
2014-09-23 | E-GEOD-61326 | biostudies-arrayexpress
Project description:Alzheimer’s disease (AD)-related degenerative decline is associated to the presence of amyloid beta (Aβ) plaque lesions and neuro fibrillary tangles (NFT). However, the precise molecular mechanisms linking Aβ deposition and neurological decline are still unclear. Here we combine genome-wide transcriptional profiling of the insular cortex of 3xTg-AD mice and control littermates from early through to late adulthood (2-14 months of age), with behavioural and biochemical profiling in the same animals to identify transcriptional determinants of functional decline specifically associated to build-up of Aβ deposits. Differential expression analysis revealed differentially expressed genes (DEGs) in the cortex long before observed onset of behavioural symptoms in this model. Using behavioural and biochemical data derived from the same mice and samples, we found that down but not up-regulated DEGs show a stronger average association with learning performance than random background genes in control not seen in AD mice. Conversely, these same genes were found to have a stronger association with Aβ deposition than background genes in AD but not in control mice, thereby identifying these genes as potential intermediaries between abnormal Aβ/NFT deposition and functional decline. Using a complementary approach, gene ontology analysis revealed a highly significant enrichment of learning and memory, associative, memory and cognitive functions only among down-regulated, but not up-regulated, DEGs. Our results demonstrate wider transcriptional changes triggered by the abnormal deposition of Aβ/NFT occurring well before behavioural decline and identify a distinct set of genes specifically associated to abnormal Aβ protein deposition and cognitive decline.
2020-11-21 | GSE161904 | GEO
Project description:Aims: While Huntington’s disease is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. Methods and Results: The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3mo of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol challenge; however, the treatment exacerbated fibrotic lesions in the heart. Gene expression analysis indicates a strong tilt toward apoptosis in the young mutant tissue as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the largest changes occurring in the cardiovascular disease and cellular metabolism clusters. Conclusions: The BACHD model of HD exhibit a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher CV risk in HD. These changes are consistent with dysfunction in ANS regulation although the hearts did respond adaptively to β-adrenergic challenge. Gene expression pattern changes are subtle but suggests biomarkers focusing on apoptosis, metabolism, immune function are worth further exploration.
2016-03-01 | GSE76593 | GEO
Project description:Vitamin D is a secosteroid that has multiple regulatory roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. Vitamin D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented the toxicity caused by human β-amyloid. Our observation that vitamin D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with a vitamin D deficiency.
2016-09-07 | GSE86493 | GEO
Project description:Non-invasive and simple methods enabling easy identification of individuals at high risk of cognitive decline are needed as preventive measures against dementia.
This pilot study aimed to explore protein biomarkers that can predict cognitive decline using urine, which can be collected noninvasively.
This prospective study demonstrated the potential for using urine to identify biomarkers of cognitive decline.
2023-03-14 | PXD039120 | JPOST Repository
Project description:The subgingival microbiome in Alzheimer's disease, mild cognitive impairment and subjective cognitive decline
| PRJEB35923 | ENA
Project description:Aims: While Huntingtonâs disease is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. Methods and Results: The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3mo of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol challenge; however, the treatment exacerbated fibrotic lesions in the heart. Gene expression analysis indicates a strong tilt toward apoptosis in the young mutant tissue as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the largest changes occurring in the cardiovascular disease and cellular metabolism clusters. Conclusions: The BACHD model of HD exhibit a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher CV risk in HD. These changes are consistent with dysfunction in ANS regulation although the hearts did respond adaptively to β-adrenergic challenge. Gene expression pattern changes are subtle but suggests biomarkers focusing on apoptosis, metabolism, immune function are worth further exploration. Microarray-based gene expression analysis in tissue from transgenic mice and controls at different ages
2016-03-01 | E-GEOD-76593 | biostudies-arrayexpress