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: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.
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: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 explore the miRNAs associated with the memory deficits in Alzheimer's disease, we detected the miRNA profiles in the hippocampus of 6-month-old male APPswe/PS1dE9 (APP/PS1) mice and age-matched wild type C57BL/6 mice.
Project description:Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer’s disease (AD), via the characterised release of IL-1β and ASC specks. However, whether NLRP3 was involved in pathways beyond this remained unknown. Here were enriched CD11b+ cells from the brains of 4, 6 an 12 month old wild-type, NLRP3-/-, APP/PS1 and APP/PS1.NLRP3-/- mice for bulk RNA sequencing. We found that amyloid deposition was associated with an increase in the expression of genes encoding inflammatory or phagocytic proteins from 6 months onwards. Interestingly, loss of NLRP3 influences glutamine/glutamate-related metabolism and increases expression of microglial Slc1a3. The increase in Slc1a3 was observed in all mice on a NLRP3-/- background and at all ages examined, demonstrating a new role for this transporter in microglia.
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:To investigate the roles of circRNAs in the microglia of AD, we isolated cortical microglia from 6-month-old male wild-type (WT) and APP/PS1 mice by MACS using a CD11b antibod and conducted a circRNA microarray to profile the circRNA expression spectrum. A total of 13420 circRNAs were detected and 218 differentially expressed circRNAs (with a fold change>1.5, P<0.05) were found. 146 circRNAs were upregulated while 72 circRNAs were downregulated in cortical microglia of APP/PS1 mice compared with WT mice.
Project description:We sought to determine the effects of Gas6 on Alzheimer’s disease pathology through overexpression of Gas6 using an adeno-associated viral vector in the APP/PS1 model of Alzheimer’s disease. 9 month old male and female APP/PS1 and nontransgenic littermates received bilateral stereotactic hippocampal injections of AAV-Gas6 or AAV-control, an attenuated Gas6 protein that does not bind the Axl receptor. One month after injections, mice performed a battery of behavioral tasks and brains were processed for immunohistochemistry, transcriptional analyses, and flow cytometry.