Project description:We isolated cerebral endothelial cells from 6-month-old WT and APP/PS1 mice and then performed In-Drop to do single cell sequencing.
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
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
Project description:Bulk RNA-sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy, in which aspects of AD-related pathology progress at different speed, shows age-dependent gene expression changes. However, bulk RNA-seq does not provide insight into the heterogeneity of expression within this cell type, particularly relevant for such models, where reactive astrogliosis is most prominent in the vicinity of plaques. To investigate astrocyte heterogeneity in ß-amyloidopathy models, we thus performed single cell RNA-sequencing on astrocytes separated by FACS.
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.
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.
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.
Project description:To examine the regulation of microglia by N-AS-triggered SPMs, we analyzed the gene expression patterns of microglia derived from WT, APP/PS1, and N-AS-injected APP/PS1 mice using RNAseq. These results indicated that N-AS-triggered SPMs activated an anti-inflammatory, positive immune response, and enhanced the phagocytic abilities of microglia in N-AS-treated APP/PS1 mice, leading to resolution of neuroinflammation and upregulation of phagocytic microglia in this AD animal model.
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.