Project description:This SuperSeries is composed of the following subset Series:; GSE14499: Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease; GSE14505: Effect of BDNF on aging-related gene expression changes in young and aged rats Experiment Overall Design: Refer to individual Series
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: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:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
Project description:While mouse models of ß-amyloidopathy recapitulate aspects of Alzheimer's disease pathology, including plaque formation and synapse loss, most progress at a speed such that outcomes are studied in the mature mouse, rather than the aged mouse. Here we investigated Aß-dependent changes to astrocytes in a knock-in model of ß-amyloidopathy (APP NL-F) that is known to progress more slowly.
Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/Ã-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Experiment Overall Design: 26 Samples total: 4 biological replicates of APP transgenic mice BDNF treated, 4 biological replicates of APP transgenic mice GFP treated, 3 biological replicates of non-trangenic mice sham lesion and 2 biological replicates of non-transgenic mice GFP treated for both tissues: Entorhinal cortex and hippocampus.
