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Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and its modulation by transcranial Direct Current Stimulation (tDCS)

ABSTRACT: Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and its modulation by transcranial Direct Current Stimulation (tDCS)

PROVIDER: PRJNA739973 | ENA |

REPOSITORIES: ENA

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Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and its modulation by transcranial Direct Current Stimulation (tDCS)

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

Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and Its Modulation by Transcranial Direct Current Stimulation (tDCS).

Project description: Not available

| S-EPMC8306644 | biostudies-literature

scRNA-sequencing of in vitro cultured ILC2 from the whole brain tissue of 7 months old 3xTg-AD and Control mice.

Project description:ILC2 are potent producers of IL-5 and IL-13 and Th2 cytokines. We have found that 3xTg-AD mice exhibit diminished ILC2 numbers and functionality in the brain barriers. We have found through scRNA-seq that cultured brain ILC2 from 7 months old 3xTg-AD mice expressed significantly less IL-5 ane Areg but increased Gzma and Gzmb.

2021-07-14 | GSE161861 | GEO

Transcriptomes of Neural Stem and Progenitor Cells from the subgranular zone (SGZ) of Wild Type (NTG) and 3xTg-AD mice at juvenile age

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

Senescent cell elimination modifies features of Alzheimer’s disease in 3xTg-AD mice

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

Single cell RNA-sequencing of NK cells from control wildtype and 3XTg-AD mice

Project description:The goal of this study is to examine the single-cell transcriptomes of NK cells from the brains of 3XTg-AD and control wildtype mice. The data generated will elucidate the transcriptomal changes of NK cells in the pro-inflammatory microenvironment of mice with Alzheimer's disease pathologies.

2020-06-08 | GSE142853 | GEO

Whole hippocampus RNA seq on (SCDi Cayman 10566) and Vehicle (DMSO) in 10 month old WT and 3xTg-AD mice

Project description:RNA was extracted from microdissected hippocampi from 10-month old DMSO or SCDi (Cayman 10566) ICV treated WT or 3xTg-AD mice.

2022-02-25 | GSE189693 | GEO

Lateral ventricle SVZ: 3xTg vs WT

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

Bulk RNA-sequencing of microglia in 3XTg-AD mice treated with anti-Nk1.1 depleting antibodies or isotype control

Project description:The goal of this experiment is to determine the effects of NK cells on microglia inflammation in 3XTg-AD mice. We examined the transcriptomal changes of microglia in mice treated with anti-NK1.1 anitbodies and isotype controls by deep RNA-Seq.

2020-06-08 | GSE142875 | GEO

Comprehensive evaluation of Ubiquinol-supplemented diet effects in the 3xTg AD mice using MALDI-MSI

Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder, accounting for up to 75 % of all dementia cases. Although the basis of AD etiology remains unknown, oxidative stress constitutes a major driver given its intimate association, specially at prodromic stages of the disease. In this line, Ubiquinol, the reduced form of coenzyme Q10, is a well-known neuroprotective antioxidant and has demonstrated significant effects in oxidative responses of β-Amyloid aggregation, internalization, and apoptosis-induced neurodegeneration. However, full extent of Ubiquinol effects in the context of AD is not yet known in detail. In this study, we designed a new methodology based on MALDI MSI for evaluating the peptide profile of the 3xTg-AD mice model fed a Ubiquinol-supplemented diet. By adopting functional analysis tools, we observed differential functional profile in hippocampus and cortex levels after 4- or 10-m o supplementation. Therefore, we also identified ACAD9, XPO1 and EIF3A as potential protein references for the diagnosis of AD at early/late stages.

2023-05-10 | PXD037763 | Pride

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