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: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:This study examined the proteome profile in the hippocampus, medial prefrontal cortex, and striatum of APPswe/PS1dE9 transgenic mice (APP/PS1) model of Alzheimer’s disease compared to wild-type mice. The effect of tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs derived from palm oil supplementation on the proteome profile of APP/PS1 mice hippocampus, medial prefrontal cortex, and striatum was also investigated. The analysis was performed using ultrahigh-performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry. This study was in hoped to understand the mechanisms of Alzheimer’s disease at proteome level, and pre-emptive activity of TRF to combat the disease.
Project description:In a series of slice electrophysiology experiments, we demonstrated that female APPSwe-Psen1dE9 Alzheimer's disease model mice show greater impairments in hippocampal synaptic plasticity than male mice of the same age and genotype. Female APP/PS1 mice also showed greater impairments in behavioural associative memory, higher amyloid plaque burden and increased microglial activation in the hippocampus than males at age 4-5 months. We thus profiled hippocampal mRNA from these mice to investigate the underlying molecular mechanisms. Compared to wild-type mice of the same sex, we found that female APP/PS1 mice showed a greater upregulation of microglial and inflammatory genes than males. Moreover, downregulation of genes associated with memory and plasticity was observed uniquely in female APP/PS1 mice. These data provide insight into the potential mechanisms of the greater prevalence and faster progression of AD in females.
Project description:Our study aimed to investigate the biological impact of forebrain neuron-specific farnesyltransferase knockout in a transgenic APP/PS1 Alzheimer's disease model.
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:This study was designed to identify and quantify pre-fibrillary proteins enriched by their insolubility in the detergent sarkosyl. Sarkosyl insoluble fractions were isolated from the brain of APP/PS1 transgenic mouse model of Alzheimer's disease and littermate wild type mice to identify protein aggregates involved in disease pathogenesis.
Project description:We performed next-generation RNA sequencing (RNA-seq) using brain tissue from 23 months old non-transgenic (NTG), non-treated and CP2 (mitochondrial complex I inhibitor)-treated APP/PS1 (mouse model of Alzheimer`s disease). By comparing transcriptomic data of NTG and vehicle-treated APP/PS1 mice, we found processes affected by the disease in APP/PS1 such as impaired ATP metabolism, ion transport, nervous system development, synaptic transmission, and inflammation. CP2-treatment in APP/PS1 positively affected genes related to immune system, axonogenesis, dendritic spine morphology, synaptic function, among the others. These data demonstrate that pathways improved by CP2 treatment in APP/PS1 mice comprise major pathways essential for therapeutic efficacy in Alzheimer`s disease.
2020-10-31 | GSE149248 | GEO
Project description:Exosomal MicroRNAs modulates the cognitive function in Fasudil treated APP/PS1 Transgenic Mouse model of Alzheimer's disease
