Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279470 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:With the criterion of 2-fold cutoff, 7 miRNAs were upregulated and 7 miRNAs were downregulated in APP/PS1 hippocampal tissues compared with WT hippocampal tissues Microarray analysis of miRNAs was performed on pooled hippocampal tissues from WT (n=16) and APP/PS1 mice (n=16) at E14
2014-01-08 | E-GEOD-53859 | biostudies-arrayexpress
Project description:NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimer’s disease (AD) at preclinical stages in cognitively normal aging populations. We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action. We found that the widely-used NSAID ibuprofen prevented early hippocampus-dependent memory deficits in APP-PS1 mice. We therefore analyzed gene expression in the hippocampus of these mice.
2016-06-14 | GSE67306 | GEO
Project description:The assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the AD-associated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA-sequencing.We identified 1690 increased AD-associated chromatin accessible regions in the hippocampal tissues of APP/PS1 mice and 1003 decreased chromatin accessible regions were considered to be related with declined AD-associated biological processes.In the APP/PS1 hippocampus, 1090 genes were found to be up-regulated and 1081 down-regulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting up-regulated mRNA levels.Our study reveals that alterations in chromatin accessibility may be an initial mechanism in AD pathogenesis.
2020-07-09 | GSE145907 | GEO
Project description:The assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the AD-associated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA-sequencing.We identified 1690 increased AD-associated chromatin accessible regions in the hippocampal tissues of APP/PS1 mice and 1003 decreased chromatin accessible regions were considered to be related with declined AD-associated biological processes.In the APP/PS1 hippocampus, 1090 genes were found to be up-regulated and 1081 down-regulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting up-regulated mRNA levels.Our study reveals that alterations in chromatin accessibility may be an initial mechanism in AD pathogenesis.
2020-07-09 | GSE145906 | GEO
Project description:In a series of slice electrophysiology experiments, we demonstrated that female APPSwe-Psen1dE9 Alzheimer's disease model mice show greater impairments in hippocampal synaptic plasticity than male mice of the same age and genotype. Female APP/PS1 mice also showed greater impairments in behavioural associative memory, higher amyloid plaque burden and increased microglial activation in the hippocampus than males at age 4-5 months. We thus profiled hippocampal mRNA from these mice to investigate the underlying molecular mechanisms. Compared to wild-type mice of the same sex, we found that female APP/PS1 mice showed a greater upregulation of microglial and inflammatory genes than males. Moreover, downregulation of genes associated with memory and plasticity was observed uniquely in female APP/PS1 mice. These data provide insight into the potential mechanisms of the greater prevalence and faster progression of AD in females.
2021-10-30 | GSE186710 | GEO
Project description:Here, we systematically investigated circRNAs in the APP/PS1 model mouse brain through deep RNA-sequencing. We report that circRNAs are markedly enriched in the brain and that several circRNAs exhibit differential expression between wild-type and APP/PS1 mice. We characterized one abundant circRNA, circTulp4, derived from Intron1 of the gene Tulp4. To investigate the effect of CircTulp4 on chromatin status, we used ATAC-seq to investigate the chromatin accessibility upon CircTulp4 knockdown.
2021-02-28 | E-MTAB-9919 | biostudies-arrayexpress
Project description:Background Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer’s disease (AD). In vitro, microglia preferentially upregulate iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo. These studies determined the effects of knocking down microglial iron import gene, Slc11a2, on AD-related cognitive decline and microglial transcriptional phenotype. Methods In vitro experiments and RT-qPCR were used to assess a role for DMT1 in amyloid-β-associated inflammation. To determine the effects of microglial Slc11a2 knockdown on AD-related phenotypes in vivo, triple-transgenic Cx3cr1Cre-ERT2;Slc11a2flfl;APP/PS1+ or – mice were generated and administered corn oil or tamoxifen to induce knockdown at 5-6 months of age. Both sexes underwent behavioral analyses to assess cognition and memory (12-15 months of age). Hippocampal CD11b+ microglia were magnetically isolated from female mice (15-17 months) and bulk RNA-sequencing analysis was conducted. Results DMT1 inhibition in vitro robustly decreased Aβ-induced inflammatory gene expression and cellular iron levels in conditions of excess iron. In vivo, Slc11a2KD APP/PS1 female, but not male, mice displayed a significant worsening of memory function in Morris water maze and a fear conditioning assay, along with significant hyperactivity compared to control WT and APP/PS1 mice. Hippocampal microglia from Slc11a2KD APP/PS1 females displayed significant increases in genes Enpp2, Ttr, and iron-export gene, Slc40a1, compared to control APP/PS1 cells. Slc11a2KD cells from APP/PS1 females also exhibited decreased expression of markers related to disease-associated microglia (DAMs), such as Apoe, Ctsb, Csf1, and Hif1α. Conclusions This work suggests a sex-specific role for microglial iron import gene Slc11a2 in propagating behavioral and cognitive phenotypes in the APP/PS1 model of AD. These data also highlight an association between loss of a DAM-like phenotype in female microglia and cognitive deficits in Slc11a2KD APP/PS1 mice. Overall, this work illuminates an iron-related pathway in microglia that may serve a protective role during disease and offers insight into mechanisms behind disease-related sex differences.
2024-07-17 | GSE269314 | GEO
Project description:NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimer's disease (AD) at preclinical stages in cognitively normal aging populations. We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action. We found that the widely-used NSAID ibuprofen prevented early hippocampus-dependent memory deficits in APP-PS1 mice. We therefore analyzed gene expression in the hippocampus of these mice. We treated male APPSwe-PS1deltaE9 mice (strain originally provided by Dr. David Borchelt and fully back-crossed to a C57BL/6J background) and their wild-type littermates with ibuprofen in chow from 3 to 6 months of age, after which we sacrificed the mice and dissected one hippocampus from each mouse for RNA isolation and microarray analysis. In each genotype-treatment group, we analyzed samples from 5 mice. Note: In our initial analysis, we found that sample GSM1644138, Hippocampus_WT_Con_rep5, was an outlier in overall gene expression. We therefore removed this sample before performing the analysis published in PMID 27190010.
2016-06-14 | E-GEOD-67306 | biostudies-arrayexpress
Project description:Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice
| PRJNA342656 | ENA
Project description:Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases. However, the initial transcriptional changes in these microglia in response to amyloid are still unknown. Here, to determine early changes in microglia gene expression, hippocampal microglia from APPswe/PS1dE9 (APP/PS1) mice and wildtype littermates were isolated and analyzed by RNA sequencing (RNA-seq). By bulk RNA-seq, transcriptomic changes were detected in hippocampal microglia from 6-months-old APP/PS1 mice. By performing single cell RNA-seq of CD11c-positive and negative microglia from 6-months-old APP/PS1 mice and analysis of the transcriptional trajectory from homeostatic to CD11c-positive microglia, we identified a set of genes that potentally reflect the initial response of microglia to Aβ.
2024-04-01 | GSE226937 | GEO