Brain Endothelial Specific IFNAR Is Key For Virus-Induced Sickness Behavior And Cognitive Impairment
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ABSTRACT:
PROVIDER: PRJNA298884 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the SubSeries listed below.
2016-04-20 | GSE74063 | GEO
Project description:Ginsenoside CK improves cognitive impairment
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Project description:Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together, these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections. Keywords: Aging, cytokines, brain, inflammation, behavior
2005-09-12 | GSE3253 | GEO
Project description:Alzheimer case-control samples originate from the EU funded AddNeuroMed Cohort, which is a large cross-European AD biomarker study relying on human blood as the source of RNA. The design is case-control. Cases are either Alzheimer's disease patients, subjects with mild cognitive impairment or age and gender matched controls.
2015-08-05 | E-GEOD-63061 | biostudies-arrayexpress
Project description:It is important to maintain cognitive integrity during underwater operations, which may also trigger cognitive alterations. Cognitive effect of underwater operations and the underlying mechanism remain elusive. Here, we found a single underwater operation affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, which was accompanied by activation of microglia and upregulation of pro-inflammatory cytokines. RNA-sequencing supported the involvement of neuroinflammation and indicated the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction. Furthermore, the upregulation of pro-inflammatory cytokines was also reversed. Mechanistically, CCR3 knockdown switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operation-induced cognitive impairment.
2024-05-20 | GSE247651 | GEO
Project description:Alzheimer's disease (AD) is a neurodegenerative disease and is the most common form of dementia, cognitive dysfunction is a pre-AD manifestation, followed by progressive deterioration in behavior and mood, CK has good pharmacological activity, inhibit neuronal damage associated with Aβ and improve learning memory in mice through its antioxidative properties. We used microarrays to detail the regulation of brain tissue genes in cognitively impaired mice by ginsenoside CK.
2023-02-10 | GSE221791 | GEO
Project description:The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). While the mechanism underlying these changes is unknown, it has been hypothesized that the presence of the amyloid precursor protein (APP) on chromosome 21 may contribute to the phenotype. Genome-wide DNA methylation abnormalities have been shown in neural tissue of patients with AD, and cells may respond to changes in gene dosage with altered DNA methylation. We therefore examined whole-genome DNA methylation in buccal epithelial cells of adults with DS to determine whether patterns of DNA methylation correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina 450K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. We found 297 CpGs to be differentially methylated between the groups, including 26 genes that were represented by more than one CpG. In addition, we found 331 probes that were correlated with cognitive function including 23 genes represented by more than one probe. We found no enrichment on chromosome 21 and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Overall, our results indicate that both Trisomy 21 and cognitive impairment are associated with distinct patterns of DNA methylation. This cohort consist of genomic DNA extracted from 20 buccal swabs, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling.
2014-01-02 | E-GEOD-50586 | biostudies-arrayexpress
Project description:Although immediate early genes (IEGs) such as Bdnf, Arc and Egr1, have been implicated in plasticity, the larger pathways related to memory and memory disorders are not well understood. Here, we combined statistical Affymetrix microarray and behavioral analyses to identify key genes and pathways associated with aging-related cognitive impairment. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal). ANOVA, linear contrasts, and overrepresentation analyses identified genes and pathways that differed from Y generally with aging (in both AU and AI) or selectively with cognitive status (only in AI or AU). Plasticity pathways, including insulin/cAMP/IEG signaling, and glycogenolytic and lipogenic pathways, were selectively downregulated (5 days) in AI, whereas Notch2 (regulating oligodendrocyte differentiation) and myelination pathways were upregulated (particularly at 21 days). Downregulation with general aging occurred in signal transduction and axonal growth/transport pathways, whereas upegulation occurred in immune/inflammatory, lipid metabolism/transport (e.g., Lxr-Srebf1), and lysosomal pathways. In AU, receptor/signal transduction genes were selectively upregulated, suggesting possible compensatory mechanisms. Immunohistochemistry confirmed and extended results to the protein level. Thus, this study identified novel cognition-linked processes, suggesting a new model in which energy-intensive, plasticity/lipogenic processes and energy-generating pathways necessary for learning are coordinately downregulated during training, while myelinogenic programs that impair cognition are concurrently activated. Keywords: Immediate Early Genes, Insulin Signaling, Cholesterol, Myelination, Glia, Inflammation, Young and Old comparaison, behavioral-characterization, Aging-related cognitive impairment.
2007-03-15 | GSE5666 | GEO
Project description:The goal of this research study is to test the feasibility of an intervention programme to reduce cognitive impairment due to cancer treatment. The investigators want to find out how acceptable the intervention and procedures are for cancer patients.
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Project description:Genome wide DNA methylation profiling of isolated human CD14+16+ monocyte and CD8+ T cell samples from HIV-infected individuals with cognitive impairment and without.
2016-10-05 | GSE87582 | GEO