Effect of small molecules on activated astrocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37611 | GEO | 2012/11/03
SECONDARY ACCESSION(S): PRJNA162319
REPOSITORIES: GEO
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Project description:We have developed an assay to test the neuroprotective properties of compounds using stem cellM-bM-^@M-^Sderived motor neurons and astrocytes, together with activated microglia as a stress paradigm. Hit compounds were discovered and the transcriptional response on activated astrocytes cells was tested. Neural stem cell (NSC)-derived astrocytes (AC) were activated with LPS and IFN-M-NM-3 and treated with hit compound for 4 hr.
2012-11-03 | E-GEOD-37611 | biostudies-arrayexpress
Project description:We have developed an assay to test the neuroprotective properties of compounds using stem cellM-bM-^@M-^Sderived motor neurons and astrocytes, together with activated microglia as a stress paradigm. Hit compounds were discovered and the transcriptional response on activated BV2 cells was tested. The BV2 cell line was activated with LPS and IFN-M-NM-3 and treated with hit compound for 4 hr.
2012-11-03 | E-GEOD-37612 | biostudies-arrayexpress
Project description:We have developed an assay to test the neuroprotective properties of compounds using stem cell–derived motor neurons and astrocytes, together with activated microglia as a stress paradigm. Hit compounds were discovered and the transcriptional response on activated BV2 cells was tested.
2012-11-03 | GSE37612 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE37611: Effect of small molecules on activated astrocytes GSE37612: Effect of small molecules on activated BV2 microglia cell line Refer to individual Series
2012-11-03 | E-GEOD-37613 | biostudies-arrayexpress
Project description:Regarding astrocytes and microglia, we are looking for pathways related with inflammatory activation, phagocytosis and vesicular/exosome trafficking. Regarding motor neurons, we are searching for pathways related with mitochondrial dynamics, Endoplasmic Reticulum stress, cell death, axonal transport, synaptic vesicles transport and oxidative stress. The general aim is to identify putative hits in ALS that relates with miR-146a expression.
2021-04-06 | PXD024294 | Pride
Project description:Type I interferons (IFN-I) are crucial for effective antimicrobial defence in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi-Goutières Syndrome and chronic viral infection. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN-I. However, the extent to which the IFN-I responses of these cells differ, if at all, is still unknown. Here we determined the global transcriptional responses of astrocytes and microglia to the IFN-I, IFN-alpha. MGCs were prepared from 2–4 day-old C57BL/6 mice. Purified primary astrocytes were obtained from the MGCs by magnetic activated cell sorting using anti-CD11b beads. Microglia were obtained from mixed glial cell cultures by mechanical shaking for 4 h. After treating astrocytes and microglia with IFN-alpha for 12 h, microarray using Affymetrix mouse genome array 430 2.0 array was performed on total RNA extracted from these cells. We found that under basal conditions, each cell type has a unique gene expression pattern reflective of its developmental origin and biological function. Following stimulation with IFN-alpha for 12 h, astrocytes and microglia also displayed a common core response that was characterized by the increased expression of genes required for pathogen detection and elimination. Microglia had a more extensive and diverse response to IFN-alpha with twice the number of genes upregulated (282 vs. 141 genes) when compared with astrocytes. Validation of the findings in vivo further suggested that astrocytes and microglia play important but distinct roles in the development of IFN-alpha-driven cerebral interferonopathies.
2018-03-18 | E-MTAB-6301 | biostudies-arrayexpress
Project description:Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction. Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we performed a transcriptional analysis on acutely isolated astrocytes and microglia from the cortex of aged controls and APPswe/PS1dE9 AD mice. As expected, both cell types acquired a proinflammatory phenotype, which confirms the validity of our approach. Interestingly, we observed that the immune alteration in astrocytes was relatively more pronounced than in microglia. Concurrently, our data reveal that astrocytes display a reduced expression of neuronal support genes and genes involved in neuronal communication. The microglia showed a reduced expression of phagocytosis and/or endocytosis genes. Co-expression analysis of a human AD expression data set and the astrocyte and microglia data sets revealed that the inflammatory changes in astrocytes were remarkably comparable in mouse and human AD, whereas the microglia changes showed less similarity. Based on these findings we argue that chronically proinflammatory astrocyte and microglia phenotypes, showing a reduction of genes involved in neuronal support and neuronal signaling, are likely to contribute to the neuronal dysfunction and cognitive decline in AD. 2 cell types from 2 conditions: cortical microglia and cortical astrocytes from 15-18 month old APPswe/PS1dE9 mice compared to wildtype littermates. Biological replicates: microglia from APPswe/PS1dE9, N=7, microglia from WT, N=7, astrocytes from APPswe/PS1dE9, N=4, microglia from WT, N=4
2015-11-04 | E-GEOD-74615 | biostudies-arrayexpress
Project description:The majority of patients with amyotrophic lateral sclerosis (ALS) have abnormal TDP-43 aggregates in the nucleus and/or cytosol of their surviving neurons and glia. Although accumulating evidence indicates that astroglial dysfunctions contribute to motor neuron degeneration in ALS, the normal physiological functions of TDP-43 in astrocytes are largely unknown and whether the loss of astroglial TDP-43 contributes to ALS remains to be clarified. Here, we showed that TDP-43 deleted astrocytes showed cell-autonomously enhanced GFAP immunoreactivity without affecting astrocyte or microglia proliferation. At the transcriptomic level, TDP-43 deleted astrocytes resemble the A1-reactive astrocytes and induce microglia to increase C1q expression. These astrocytic changes do not cause the loss of motor neurons in spinal cords or denervation at the neuromuscular junctions. In contrast, there was a selective reduction of mature oligodendrocytes, but not oligodendrocyte precursor cells, suggesting a tri-glial dysfunction mediated by TDP-43-deleted astrocytes. Mice with astroglial TDP-43 deletion developed motor, but not sensory, deficits. Taken together, our results demonstrate that TDP-43 is required to maintain the protective functions of astrocytes relevant to the development of motor deficits in mice.
2020-11-01 | GSE156542 | GEO
Project description:Microglia, brain resident macrophages, require instruction from the central nervous system microenvironment to maintain their identity, morphology, and to regulate inflammatory responses. We investigated the heterogeneity of response of microglia to the presence of neurons and astrocytes by performing single-cell sequencing of microglia in both monoculture, and in coculture with neurons and astrocytes.
2021-03-23 | E-MTAB-10030 | biostudies-arrayexpress
Project description:GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease. Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation. 2 cell types from 6 conditions: cortical microglia and cortical astrocytes from 15-18 month old APPswe/PS1dE9 mice compared to wildtype littermates. Biological replicates: microglia from APPswe/PS1dE9, N=7, microglia from WT, N=7, astrocytes from APPswe/PS1dE9, N=4, microglia from WT, N=4
2015-11-04 | E-GEOD-74614 | biostudies-arrayexpress