Hypoxia differentially accelerates cognitive impairment related features in cerebral cortex revealed by single cell sequencing in APP/PS1 mice
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PROVIDER: PRJNA809204 | ENA |
REPOSITORIES: ENA
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Project description:Here we aimed at exploring the effect of hypoxia on cognitive impairment progression in a single cell resolution through single cell RNA sequencing (ScRNA seq). We exposed the APP/SP1 transgenic AD model mice to hypoxia condition and explored the cell heterogeneity and interactions in cerebral cortex with single cell RNA sequencing (10X genomics). We further analyze the differently expressed genes and signaling pathways related with cognitive impairment by different cell types and subclusters.
2025-09-01 | GSE197151 | GEO
Project description:RNA samples from the cerebral cortex of APP/PS1 and WT mouse littermates aged 3, 6 and 12 months were analyzed using the Affymetrix Genechip Mouse Gene 1.1 ST Array. The APP-PS1 transgenic mouse express the human mutated forms APPswe and PS1dE9. This is a good model of familial Alzheimer Disease because it reproduces several features of the disease as β-amyloid deposits throughout the brain and exhibit memory impairment by the end of the sixth month and is a simple model to study the molecular pathways. The aim of this study is to identify dysregulation of inflammation pathways in order to understand shifts of inflammation responses with disease progression.
2014-04-30 | E-MTAB-2121 | biostudies-arrayexpress
Project description:Affects of ADAM17 AAV9 mediated injection on cognitive and vascular function in the APP/PS1 mouse model of Alzheimer's disease.
2023-03-02 | PXD040026 | Pride
Project description:Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic endfeet. Loss of AQP4 polarization is associated with many diseases. In Alzheimer's disease (AD), it is found that AQP4 loos its normal location and thus reduce the clearance of amyloid-β plaques and Tau protein. Clinical and experimental studies show that moxibustion can improve the learning and memory abilities of AD. In order to explore whether moxibustion can affect the polarization of AQP4 around blood brain barrier (BBB), we used spatial transcriptomics (ST) to analyze the expression and polarization of Aqp4 in wild type mice, APP/PS1 mice and APP/PS1 mice intervened by moxibustion. The results showed that moxibustion improved the loss of abnormal polarization of AQP4 in APP/PS1 mice, especially in the hypothalamic BBB. Besides, there are other 31 genes with Aqp4 as the core have the similar depolarization in APP/PS1 mice, most of which are also membrane proteins. The majority of them have been reversed by moxibustion. At the same time, we employed the cerebrospinal fluid circulation gene set, which was found being on a higher level in the group of APP/PS1 mice with moxibustion treatment. Finally, in order to further explore its mechanism, we analyzed the mitochondrial respiratory chain complex enzymes closely related to energy metabolism, and found that moxibustion can significantly increase the expression of mitochondrial respiratory chain enzymes such as Cox6a2 in the hypothalamus, which could provide energy for mRNA transport. Our research shows that increasing the polarization of hypothalamic Aqp4 through mitochondrial energy supply may be an important target for moxibustion to improve APP/PS1 mice’s cognitive impairment.
2023-02-22 | GSE222981 | GEO
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:An antisense oligonucleotide (ASO) against E3 ubiquitin ligase IDOL in the brain significantly decreased Aβ pathology, and improved spatial learning and memory in APP/PS1 mice.
2019-12-24 | GSE142535 | GEO
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:NLRP3 inflammasome activation is involved in the progression of Alzheimer's disease. To unravel the unique cell populations and clusters regulated by NLRP3 in the brain, we enriched CD11b+ cells from the brains of 18 month old wild-type, NLRP3-/-, APP/PS1 and APP/PS1.NLRP3-/- mice for single cell RNAseq.
2025-02-03 | GSE271192 | GEO
Project description:The goal of the experiment was to understand the role of IL-18 in Alzheimers disease. Gene expression was examined in the hippocampus of wild type mice and the APP/PS1 mice (which are a mouse model for Alzheimers disease) that either encoded IL-18 or had the IL-18 gene knocked out.
2017-12-31 | E-MTAB-5668 | biostudies-arrayexpress
Project description:To identify the differentially expressed genes in the brain of WT mice in comparison with 9-month-old APP/PS1 mice, we examined the microarray gene expression profile of the groups above. Neuroinflammation is well implicated in the progression of Alzheimer’s Disease (AD) now. What’ more, neuroinflammation is supposed to be one of the essential trigger to induce neurodegeneration. In this study, we examined the differentially expressed genes (including coding transcripts and lncRNA) between the wild type (WT) mouse and a AD model, the APP/PS1 mouse. We found that, among all these P2XR family genes, P2X7R is not only the most abundant expressed, but also identified as the highest upregulated gene. The elevated P2X7R expression promotes neuroinflammation through activation of NLRP3 inflammsome, and further mediate one kind of inflammatory cell death, pyroptosis. Blockade of P2X7R could not only inhibit pyroptosis, but also could mildly alleviate cognitive deficits in APP/PS1 mice. Our study provides new insight into an alternative strategy for the development of AD therapy.
2021-01-01 | GSE109479 | GEO