Lab4-3xtg
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB63202 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women are not only nearly twice as likely to develop Alzheimer’s, but they also experience worse neuropathological burden and cognitive decline despite living longer with the disease. It remains unclear how and when sex differences in biological aging emerge and contribute to Alzheimer’s disease pathogenesis. We hypothesized that these differences lead to distinct molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development. We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans while longitudinally collecting brain samples. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes between 3xTg-AD and B6129 samples and across ages in each sex. 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females, especially in genes involved in complement system activation, suggesting distinct inflammatory disease trajectories between the sexes. Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, revealing that age-related changes in immune response act as a primary driver of sex differences in Alzheimer’s disease trajectories.
2024-07-08 | GSE254970 | GEO
Project description:The 3xTg-AD mouse is a widely used model in the study of Alzheimer’s Disease (AD). It has been extensively characterized both from the anatomical and behavioral point of view but poorly studied at the transcriptomic level. For the first time, this study characterizes the whole blood transcriptome of the 3xTg-AD mouse at three and six months of age and evaluates how gene expression is modulated by transcranial direct current stimulation (tDCS). RNA-seq analysis revealed 183 differentially expressed genes (DEGs) that were a direct signature of the genetic background of the mouse. The expression profile of age-related genes in the 3 months-old 3xTg-AD mice was more similar to that of 6 months rather than 3 months-control mice, suggesting a premature aging of the 3xTg-AD mice. Moreover, in the 6 months-old 3xTg-AD mice, we observed a high number of DEGs that could represent good peripheral biomarkers of AD progression. Finally, tDCS was associated with gene expression changes in the 3xTg-AD but not in the control mice. In conclusion, this study provides a better molecular characterization of the 3xTg-AD mouse and suggests that blood gene expression can be used to identify new biomarkers of AD progression and treatments effect.
2021-07-19 | GSE178662 | GEO
Project description:Cellular senescence has been associated with neurodegenerative disease and clearance of senescent cells using genetic or pharmaceutical strategies (senolytics) has demonstrated beneficial effects in mouse models investigating individual disease etiologies of Alzheimer’s disease (AD). However, it has remained unclear if senescent cell clearance in a mouse model exhibiting both plaque and tau pathologies modifies the disease state (3xTg). Here, we show that treatment with senolytics (ABT263 (navitoclax) or a combination of dasatinib and quercetin (D+Q)) or transgenic removal of p16-expressing cells (via INK-ATTAC) reduced microgliosis and ameliorated both amyloid and tau pathology in 3xTg mice. Using RNA sequencing, we found evidence that synaptic dysfunction and neuroinflammation was attenuated with senescent cell removal. Unfortunately, these beneficial effects were not seen with short-term senolytic treatment in mice with more advanced disease. Overall, our results further corroborate the beneficial effects senescent cell clearance could have on AD and highlight the importance of early intervention for treatment of this debilitating disease.
2024-03-20 | GSE231332 | GEO
Project description:Transcriptional profiling of the microdissected SVZ from 7-month-old mice Adult neurogenesis is suppressed in the SVZ of 3xTg mice, a model of Alzheimer's disease. To better understand the underlying mechanisms of this suppression, the goals of this experiment were to compare the transcriptional profiles of the SVZ neural stem cell niche in 3xTg-AD mice versus strain controls. We used early middle-aged mice (7-months-old) rather than old mice, in order to identify genetic changes that are not caused secondarily to other degenerative changes occurring in these mice. Two-condition experiment, 3xTg vs WT SVZ. Biological replicates: 4 for each.
2015-08-01 | E-GEOD-60460 | biostudies-arrayexpress
Project description:The goals of this study are to compare transcriptome profiling (RNA-seq) in wild-type (NTG) and 3xTg-AD mice, to determine the transcriptomal changes of neural stem and progenitor cells (NSPC) from the SGZ at early stages of Alzheimer's Disease in a mouse model. Methods: A tamoxifen (TAM)-inducible Nestin-CreERT2;ROSA26-EYFP reporter mouse line was cross-bred with NTG or 3xTG-AD mice to label NSPC upon TAM administration. YFP-positive NSPCs were sorted through FACS (Fluorescence-Activated Cell Sorting) 10 days after TAM from NTG; Nestin-CreERT2;ROSA26-EYFP and 3xTg-AD;Nestin-CreERT2;ROSA26-EYFP mice. RNA was extracted with RNeasy Micro Kit and deep-sequenced on the NovaSeq SP flowcell SR200 platform. The sequence reads of Fastq files that passed quality filters were aligned to the mouse genome (build mm10) using hisat2. Samtools was used to index the BAM files. DESeq2 was used to establish differential gene expression between NTG and 3xTg-AD samples. Results: We mapped about 48 million sequence reads per sample to the mouse genome (build mm10) and identified 1391 genes that were differentially expressed in the 3xTg-AD, with 720 down- and 671 up-regulated. Genes were considered significantly different between two genotypes if they meet the following criteria: 1) adjusted p-value < 0.05, and 2) log2 fold change > 0.5 or < -0.5. Conclusions: Gene ontology analysis of differentially expressed genes uncovered several pathways that may contribute to early neural stem cell decline in the 3xTg mice. Our results revealed very early perturbations in the SGZ neurogenic niche in the 3xTg mouse model of AD, manifested by intrinsic molecular changes in neural stem and progenitor cells (NSPC) at juvenile age, resulting in dysregulated neural stem cell homeostasis.
2023-02-15 | GSE218323 | GEO
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:A large scale profiling of 3xtg mouse brain to invetigate the AD proteomic phenotype.
2024-06-25 | PXD053314 | Pride
Project description:We profiled REST targets in WT mice, as well as the Alzheimer’s disease 3xTg mouse model, to gain insight into the regulation of physiological pathways by REST, as well as the altered REST cistrome in Alzheimer’s disease.
2022-01-29 | GSE195446 | GEO
Project description:Transcriptional profiling of the microdissected SVZ from 7-month-old mice Adult neurogenesis is suppressed in the SVZ of 3xTg mice, a model of Alzheimer's disease. To better understand the underlying mechanisms of this suppression, the goals of this experiment were to compare the transcriptional profiles of the SVZ neural stem cell niche in 3xTg-AD mice versus strain controls. We used early middle-aged mice (7-months-old) rather than old mice, in order to identify genetic changes that are not caused secondarily to other degenerative changes occurring in these mice.
2015-08-01 | GSE60460 | GEO
Project description:Senescent cell elimination modifies features of Alzheimer’s disease in 3xTg-AD mice
| PRJNA963864 | ENA