Project description:The APPSwe/PS1dE9 (APP/PS1) mouse ß-amyloidopathy mouse model exhibits extracellular Aß deposition, particularly in the neocortex and hippocampus, increasing steadily from about 6 months, with reactive astrogliosis and synapse loss occurring proximal to plaques. We crossed APP/PS1 mice onto genetically modified mice which lack microglia (Csf1r ∆FIRE/∆FIRE) to assess whether Aß plaque deposition and downstream events are altered in brains lacking microglia.
Project description:The APPSwe/PS1dE9 (APP/PS1) ß-amyloidopathy mouse model exhibits extracellular Aß deposition increasing steadily from about 6 months, particularly in the neocortex and hippocampus, with reactive astrogliosis and synapse loss occurring proximal to plaques. We crossed APP/PS1 mice onto genetically modified mice which lack microglia (Csf1r ∆FIRE/∆FIRE) to assess whether Aß plaque deposition and downstream events are altered in brains lacking microglia.
Project description:The assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the AD-associated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA-sequencing.We identified 1690 increased AD-associated chromatin accessible regions in the hippocampal tissues of APP/PS1 mice and 1003 decreased chromatin accessible regions were considered to be related with declined AD-associated biological processes.In the APP/PS1 hippocampus, 1090 genes were found to be up-regulated and 1081 down-regulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting up-regulated mRNA levels.Our study reveals that alterations in chromatin accessibility may be an initial mechanism in AD pathogenesis.
Project description:The assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the AD-associated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA-sequencing.We identified 1690 increased AD-associated chromatin accessible regions in the hippocampal tissues of APP/PS1 mice and 1003 decreased chromatin accessible regions were considered to be related with declined AD-associated biological processes.In the APP/PS1 hippocampus, 1090 genes were found to be up-regulated and 1081 down-regulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting up-regulated mRNA levels.Our study reveals that alterations in chromatin accessibility may be an initial mechanism in AD pathogenesis.
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:In order to disclose the mechanisms, a high-throughput quantitative proteomics analysis was established to investigate the proteome profiles changes of hippocampus and temporal lobe of WT mice, APP/PS1 mice and rapamycin treated APP/PS1 mice.The extraction of proteins of hippocampus and temporal tissue employed liquid nitrogen grounding method, which was described as previous works of our laboratory and other laboratories [20, 21]. After fully and immediately grinding under the protection of liquid nitrogen, the products was dissolved by lysis buffer (8 M urea and 1 cocktail in PBS, pH = 8.0) prepared in ice ahead of schedule and then the solutions were transferred to a 1.5-mL tube in ice. Cellular debris was removed by centrifugation (12,000 rpm, 15 min, 4 °C) and the liquid supernatant was transferred into a fresh 1.5-mL tube and immediately stored at -80 °C. The protein concentration of the supernatant was detected by Nanodrop 2000 (Thermo Scientific, NJ, USA) following the manufacture instructions.
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:Muscle secretes factors during exercise that enhance cognition. Myokine Cathepsin B (Ctsb) is linked to memory, but its role in neurodegeneration is unclear. Here we show that AAV-vector-mediated Ctsb overexpression in skeletal muscle, in an Alzheimer’s Disease (AD) mouse model (APP/PS1), improved motor coordination, memory and adult hippocampal neurogenesis, while plaque density was unchanged. Conversely, in wildtype (WT) mice Ctsb impaired memory. To understand underlying mechanisms, hippocampus, muscle and plasma proteomic analyses were performed. In AD mice, Ctsb treatment increased abundance of hippocampal proteins involved in mRNA metabolism and protein synthesis. In muscle, Ctsb treatment increased protein translation in AD mice, whereas in WT mitochondrial proteins decreased. Additionally, in AD mice Ctsb enhanced plasma metabolic and mitochondrial processes, and reduced inflammatory responses. The differing protein abundance profiles in the AD and WT treatment groups correspond to effects on memory function. Overall, skeletal muscle Ctsb expression is a potential AD therapeutic.
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.