Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA379222 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic alterations has been implicated in the pathology of several neurodegenerative diseases. To investigate the role of microglial Hdac1 and 2 in the pathogenesis of Alzheimer's disease (AD), we created microglia specific compound Hdac1 and Hdac2 knock out mice in 5X FAD background. Genetic ablation of Hdac1 and 2 from microglia reduced amyloid plaque burden and improved spatial learning and memory function. To study how Hdac1 and 2 knock out in microglia alters gene expression profile in 5X FAD mice we carry out microarray analysis using 24-28 weeks animals
2018-03-14 | GSE96622 | GEO
Project description:We created a novel murine model of Alzheimer's Disease using a knock-in strategy to humanize the sequence of the murine App gene and introduced three familial AD (FAD) mutations, Swedish (Swedish (KM670/671NL), Arctic (E693G)) and Austrian (T712I). We characterized the effects of these genetic modifications on the transcriptome of FACS-isolated microglia from 8-month-old App-SAA mice. Numerous genes were differentially expressed between cells from homozygous App-SAA animals compared to those from WT littermates. For example, we observed up-regulation of Disease-associated microglia (DAM) genes. In contrast, the transcriptome of microglia from heterozygous App-SAA animals broadly resembles that of their WT counterparts.
2021-01-20 | GSE158152 | GEO
Project description:We created a novel murine model of Alzheimer's Disease using a knock-in strategy to humanize the sequence of the murine App gene and introduced three familial AD (FAD) mutations, Swedish (Swedish (KM670/671NL), Arctic (E693G)) and Austrian (T712I). To determine whether App-SAA microglia exhibit cellular dysfunctions and whether these dysfunctions relate to fibrillar Ab internalization, mice were intraperitoneally (i.p.) injected with 10 mg/kg methoxy-X04. 24 hours after injection, mice were perfused with PBS, cortical and hippocampal tissues were dissected and processed into single-cell suspension and methoxy-X04-negative and methoxy-X04-positive microglia were isolated using FACS. Mirroring our gene expression studies, we found profound alterations of the AppSAA microglia transcriptome; these changes were exacerbated in methoxy-X04 positive compared to negative cells.
2021-01-20 | GSE158153 | GEO
Project description:Hdac1 and 2 are important regulators of developmental processes. In this study we created microglia specific compound Hdac1 and Hdac2 knock out mice. Pre-natal ablation of both Hdac1 and 2 from microglia leads to reduced cell number and altered cell morphology. To investigate how Hdac1 and 2 knock out in microglia alters cellular gene expression profile we carried out RNA-seq analysis at different time points.
2018-03-14 | GSE98822 | GEO
Project description:Transcription profiling by array of microglia purified from wild type and TREM2 deficient microglia in a mouse model of Alzheimer's disease
2016-06-30 | E-GEOD-65067 | ExpressionAtlas
Project description:Alzheimer’s disease (AD) is the most common neurodegenerative dementia. Around 10% of cases present an age of onset before 65 years-old, which in turn can be divided in monogenic or familial AD (FAD) and sporadic early-onset AD (EOAD). Mutations in PSEN1, PSEN2 and APP genes have been linked with FAD. The aim of our study was to describe the brain whole-genome RNA expression profile of the posterior cingulate area in EOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). 14 patients (7 EOAD and 7 FAD-PSEN1) and 7 neurologically healthy controls were selected and samples were hybridized in a Human Gene 1.1 microarray from Affymetrix. When comparing controls with EOAD and controls with FAD-PSEN1, we found 3183 and 3351 differentially expressed genes (DEG) respectively (FDR corrected p<0.05). However, any DEG was found in the comparison of the two groups of patients. Microarrays were validated through quantitative-PCR of 17 DEG. In silico analysis of the DEG revealed an alteration in biological pathways related to calcium-signaling, axon guidance and long-term potentiation (LTP), among others, in both groups of patients. These pathways are mainly related with cell signalling cascades, synaptic plasticity and learning and memory processes. In conclusion, the altered biological final pathways in EOAD and FAD-PSEN1 are highly coincident. Also, the findings are in line with those previously reported for late-onset AD (LOAD, onset >65 years-old), which implies that the consequences of the disease at the molecular level are similar in the final stages of the disease. 21 Samples were analyzed: 7 controls, 7 Early-onset Alzheimer's disease (AD) patients and 7 early-onset AD genetically determined by a mutation in PSEN1 gene.
2015-01-20 | E-GEOD-39420 | biostudies-arrayexpress
Project description:Epigenetic dysregulation, which leads to the alteration of gene expression in the brain, is suggested as one of the key pathophysiological bases of aging and neurodegeneration. Here we found that, in the late-stage familial Alzheimer’s disease (FAD) mouse model, repressive histone H3 dimethylation at lysine 9 (H3K9Me2) and euchromatic histone methyltransferases, EHMT1 and EHMT2 (H3K9Me2 catalyzer), were significantly elevated in the prefrontal cortex (PFC) region of post-mortem tissues from human patients with Alzheimer's disease. Concomitantly, H3K9Me2 at the promoter region of glutamate receptors was increased in PFC of aged FAD mice, which was linked to the diminished transcription, expression and function of AMPA and NMDA receptors. Treatment of FAD mice with specific EHMT1/2 inhibitors reversed histone hyper-methylation and led to the recovery of glutamate receptor expression and excitatory synaptic function in PFC and hippocampus. Chromatin immunoprecipitation-sequencing (ChIP-seq) data indicated that FAD mice exhibited genome-wide increase of H3K9Me2 enrichment at genes involved in neuronal signaling (including glutamate receptors), which was reversed by EHMT1/2 inhibition. Moreover, the impaired recognition memory, working memory, and spatial memory in aged FAD mice were rescued by the treatment with EHMT1/2 inhibitors. These results suggest that disrupted epigenetic regulation of glutamate receptor transcription underlies the synaptic and cognitive deficits in Alzheimer's disease, and targeting histone methylation enzymes may represent a novel therapeutic strategy for this prevalent neurodegenerative disorder.
2019-01-30 | GSE125850 | GEO
Project description:Transcription profiling by array of embryonic stem cells from wild type and histone deacetylase 1 (HDAC1) knock out mice
2014-07-03 | E-GEOD-5583 | ExpressionAtlas
Project description:Neuronal expression of Alzheimer's disease-associated FAD mouse genotype at 3/6/12 months.
2019-12-04 | GSE140286 | GEO