Systemic inflammation modulates Fc receptor expression on microglia in chronic neurodegeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Katie Lunnon
PROVIDER: E-GEOD-23182 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The experiment describes the dynamic transcriptional alterations in brains of ME7- infected, and age-matched, mock-inoculated mice immediatly before inoculation, at two important preclinical time points and at terminal stages.
2007-05-04 | E-MEXP-1005 | biostudies-arrayexpress
Project description:To investigate the inflammatory response in neurodegenerative disease during an episode of systemic inflammation using the ME7 prion model. Comparison of ME7-infected mice with mice innoculated with Normal brain homogenate (NBH). 18 weeks post-innoculation mice were administered 500ug/kg LPS or an equivalent volume of saline as a control.
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Project description:A study of differential gene expression in the hippocampus of CV mice (C57Bl x VM/Dk) inoculated with ME7 scrapie to determine the molecular events that accompany the scrapie-associated hippocampal neuropathology. Analysis was performed at 170 days post infection, a timepoint that coincides with severe hippocampal neuronal loss.
2005-05-01 | E-MEXP-284 | biostudies-arrayexpress
Project description:Prion infection results in progressive neurodegeneration of the central nervous system invariably resulting in death. The pathological effects of prion diseases in the brain are morphologically well defined, such as gliosis, vacuolation, and the accumulation of disease-specific protease-resistant prion protein (PrPSc). However, the underlying molecular events that lead to the death of neurons are poorly characterised. In this study cDNA microarrays were used to profile gene expression changes in the brains of two different strains of mice infected with three strains of mouse-adapted scrapie. Extensive data was collected and analyzed, from which we identified a core group of 349 prion-related genes (PRGs) that consistently showed altered expression in mouse models. Gene ontology analysis assigned many of the up-regulated genes to functional groups associated with one of the primary neuropathological features of prion diseases, astrocytosis and gliosis; protein synthesis, inflammation, cell proliferation and lipid metabolism. Using a computational tool, Ingenuity Pathway Analysis (IPA), we were able to build networks of interacting genes from the PRG list. The regulatory cytokine TGFB1, involved in modulating the inflammatory response, was identified as the outstanding interaction partner for many of the PRGs. The majority of genes expressed in neurons were down-regulated; a number of these were involved in regulatory pathways including synapse function, calcium signalling, long-term potentiation and ERK/MAPK signalling. Two down-regulated genes coding for the transcription regulators, EGR1 and CREB1, were also identified as central to interacting networks of genes; these factors are often used as markers of neuronal activity and their deregulation could be key to loss of neuronal function. These data provides a comprehensive list of genes that are consistently differentially expressed in multiple scrapie infected mouse models. Building networks of interactions between these genes provides a means to understand the complex interplay in the brain during neurodegeneration. Resolving the key regulatory and signaling events that underlie prion pathogenesis will provide targets for the design of novel therapies and the elucidation of biomarkers. Keywords: disease state analysis C57BL/6 mice were inoculated by intracerebral infection of brain homogenate from mice clinically infected with the ME7, 79a and 22A strains of scrapie. In addition VM mice were also inoculated with the 22A scrapie strain. Mice were sacrificed at the onset of clinical diseases as manifested by uncoordinated gait, flaccid paralysis of the hind limbs, rigidity and abolishment of the righting reflex. Brain tissue was collected from these mice and the RNA isolated. Mouse CNS gene expression was analysed by two-colour microarray experiments using an in house manufactured 11K mouse cDNA microarray. RNA from individual infected mice was hybridized to each array versus pooled reference RNA from an equivalent number of age-matched, mock-infected control mice. In total we hybridized 34 different samples to microarrays in this experiment; 8-10 individual mice from each of the four sample groups were individually processed for separate microarrays. Hierachical clustering shows that the patterns of gene expression are for the most part common to the different mouse models . We used the program EDGE to identify genes that were differentially expressed in mouse brain during clinical disease. We used a P value cut-off of 0.05 as the criteria for selection of significantly differentially expressed genes. A similar design was used to determine gene expression profiles from C57BL/6 mice infected with a fourth strain of scrapie, RML. Total RNA from three mice, plus dye swaps, was hybridized to Agilent whole genome mouse arrays to validate genes identified using our manufactured BMAP arrays.
2010-05-26 | E-GEOD-10310 | biostudies-arrayexpress
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Project description:Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy (AI) is an approach that involves administration of antiviral T cells and has shown promise in clinical studies for the treatment of peripheral virus infections in humans such as cytomegalovirus, Epstein-Barr virus, and adenovirus, among others. Clearance of neurotropic infections, on the other hand, is particularly challenging because the central nervous system (CNS) is relatively intolerant of immunopathological reactions. Therefore, it is essential to develop and mechanistically understand therapies that noncytopathically eradicate pathogens from the CNS. Here, we used mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV) to demonstrate that therapeutic antiviral T cells can completely purge the persistently infected brain without causing blood brain barrier breakdown or tissue damage. Mechanistically, this is accomplished through a tailored release of chemoattractants that recruit antiviral T cells, but few pathogenic innate immune cells such as neutrophils and inflammatory monocytes. Upon arrival, T cells enlisted the support of nearly all brain resident myeloid cells (microglia) by converting them into CD11c+ antigen-presenting cells (APCs) – a cell population also found in the brain of a human immunodeficiency virus infected patient. Two-photon imaging studies revealed that antiviral CD8+ and CD4+ T cells interacted directly with CD11c+ microglia and induced STAT1 signaling, but did not initiate programmed cell death. We propose that noncytopathic CNS viral clearance can be achieved by therapeutic antiviral T cells reliant on restricted chemoattractant production and interactions with apoptosis-resistant microglia. 6 Mouse Microglia-sorted Brain Samples: 3 (-) AI, 3 (+) AI.
2015-06-22 | E-GEOD-66421 | biostudies-arrayexpress
Project description:The light-organ symbiosis between the squid Euprymna scolopes and the luminous bacterium Vibrio fischeri offers the opportunity to decipher the hour-by-hour events that occur during the natural colonization of an animal's epithelial surface by its microbial partners. To determine the genetic basis of these events, a glass-slide microarray was used to characterize the light-organ transcriptome of juvenile squid in response to the initiation of symbiosis. Patterns of gene expression were compared between animals not exposed to the symbiont, exposed to the wild-type symbiont, or exposed to a mutant symbiont defective in either of two key characters of this association: bacterial luminescence or autoinducer (AI) production. Hundreds of genes were differentially regulated as a result of symbiosis initiation, and a hierarchy existed in the magnitude of the host's response to three symbiont features: bacterial presence > luminescence > AI production. Putative host receptors for bacterial surface molecules known to induce squid development are up-regulated by symbiont light production, suggesting that bioluminescence plays a key role in preparing the host for bacteria-induced development. Further, because the transcriptional response of tissues exposed to AI in the natural context (i.e., with the symbionts) differed from that to AI alone, the presence of the bacteria potentiates the role of quorum signals in symbiosis. Comparison of these microarray data with those from other symbioses, such as germ-free/conventionalized mice and zebrafish, revealed a set of shared genes that may represent a core set of ancient host responses conserved throughout animal evolution. Six experimental treatments of juvenile animals were performed for the microarray matrix: uncolonized (Apo); uncolonized, but supplemented with AI (Apo + AI); colonized by wild-type V. fischeri (wild type); colonized by a mutant defective in luciferase synthesis (luxA); colonized by a mutant defective in AI synthesis (luxI); and, colonized by the luxI mutant, but supplemented with AI (luxI + AI). At 18 h postinoculation, animals were anesthetized in 2% ethanol in HOSW, and the light organs were removed into RNAlater (Ambion Biosystems).
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