Expression data from mouse optic nerve head after elevation in intraocular pressure
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE40009 | GEO | 2013/05/17
SECONDARY ACCESSION(S): PRJNA172339
REPOSITORIES: GEO
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Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.
2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress
Project description:Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation. Young adult male mice underwent middle cerebral artery occlusion (MCAO) to produce ischemic stroke or control sham surgery. Young adult mice were injected intraperitoneally with 5 mg/kg lipopolysaccharide (LPS) to produce neuroinflammation or saline for control. Astrocytes were acutely purified from control and injured brains at 1 day after injury for LPS/saline injection and 1, 3 days and 7 days after MCAO/sham surgeries.
2012-05-01 | E-GEOD-35338 | biostudies-arrayexpress
Project description:Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
2012-05-02 | GSE35338 | GEO
Project description:Following contusive spinal injury astrocytes undergo inflammatory activation and proliferation in a process known as astrogliosis. Reactive astrocytes are attractive therapeutic targets as they sit central to many of the immune recruitment, injury response, and tissue healing processes of the spinal cord. However, methods of targeted expression of exogenous therapeutic genes within astrocytes must be validated to not alter the normal immunological involvement of astrocytes. To investigate the effect of transgene expression within astrocytes upon the immunological state of the contused cord, we injected the astrocyte-selective AAV5-GfaABC1D-dYFP reporter vector into an animal model of moderate contusive spinal cord injury. Bulk RNA microarrays were used to assess transcriptomic changes of the perilesional tissue.
2021-08-26 | GSE182796 | GEO
Project description:Astrocytes are the predominant component of the scar and play crucial roles in spinal cord injury (SCI) at acute injury stage. Understanding the complex reactive astroglial contributions to SCI pathophysiologies is important for developing therapeutic strategies. To understand the mechanisms of astrogliosis in SCI, and to identify novel molecular targets to improve the injury environment and axonal regeneration, we have studied gene expression changes in SCI epicenter tissue using RNA-Seq at chronic stages (1 month and 3 months) in mouse moderate contusive injury models. Importantly, we have also FACS purified cells successfully from adult spinal cord using transgenic mice and generated RNA-Seq results for both acute (7 days) and chronic (1 month and 3 months) injury stages. The SCI RNA-Seq analysis provided valuable information on the gene expression in injury environment and astrocytes after SCI. In addition to protein coding genes, we were the first to systematically analyze the expression profiles of Long Noncoding RNAs (lncRNAs) in SCI and purified astrocytes. We have tested a number of candidates and found gene of interest Zeb2os which is a highly conserved lncRNA in human. Zeb2os expression has high correlation with an essential transcription factor (TF) in astrogliosis, Stat3, and its antisense protein coding gene Zeb2. Furthermore, our ChIP-seq experiment showed STAT3 bound to Zeb2 promoter region, thus Zeb2os may regulate Zeb2 and Stat3 directly or indirectly and STAT3 may regulate Zeb2 expression. Moreover, we have demonstrated for the first time by shRNA gene knockdown (KD) and functional assays that Zeb2os plays an important functional role in astrogliosis. We found Zeb2os KD in primary astrocytes affected a number of downstream genes by RNA-Seq, for example, Gfap, Zeb2, and Stat3 level decreased and reduced astrocyte proliferation.
2021-02-08 | GSE153720 | GEO
Project description:Astrocytes are the predominant component of the scar and play crucial roles in spinal cord injury (SCI) at acute injury stage. Understanding the complex reactive astroglial contributions to SCI pathophysiologies is important for developing therapeutic strategies. To understand the mechanisms of astrogliosis in SCI, and to identify novel molecular targets to improve the injury environment and axonal regeneration, we have studied gene expression changes in SCI epicenter tissue using RNA-Seq at chronic stages (1 month and 3 months) in mouse moderate contusive injury models. Importantly, we have also FACS purified cells successfully from adult spinal cord using transgenic mice and generated RNA-Seq results for both acute (7 days) and chronic (1 month and 3 months) injury stages. The SCI RNA-Seq analysis provided valuable information on the gene expression in injury environment and astrocytes after SCI. In addition to protein coding genes, we were the first to systematically analyze the expression profiles of Long Noncoding RNAs (lncRNAs) in SCI and purified astrocytes. We have tested a number of candidates and found gene of interest Zeb2os which is a highly conserved lncRNA in human. Zeb2os expression has high correlation with an essential transcription factor (TF) in astrogliosis, Stat3, and its antisense protein coding gene Zeb2. Furthermore, our ChIP-seq experiment showed STAT3 bound to Zeb2 promoter region, thus Zeb2os may regulate Zeb2 and Stat3 directly or indirectly and STAT3 may regulate zeb2 expression. Moreover, we have demonstrated for the first time by shRNA gene knockdown (KD) and functional assays that Zeb2os plays an important functional role in astrogliosis. We found Zeb2os KD in primary astrocytes affected a number of downstream genes by RNA-Seq, for example, Gfap, Zeb2, and Stat3 level decreased and reduced astrocyte proliferation.
2021-02-08 | GSE153085 | GEO
Project description:Astroglia, the star-shaped cells found throughout the central nervous system are the most numerous cell type in the brain. The astroglial response to injury, generically termed reactive astrogliosis, is classically defined by cellular hypertrophy and process extension, increased glial filament production, and some degree of proliferation. Astrogliosis and its functional outcomes, glial scar formation and neuroinflammation, are often viewed as detrimental to recovery. However, increasing evidence points to neuroprotective roles of reactive astroglia in the setting of brain injury. Therapeutic modulation of this double-edged sword will require detailed knowledge of mechanisms by which specific signals induce detrimental and beneficial phenotypes. This proposal is is a logical extension of a published, peer reviewed study (Heffron DS and Mandell JW, Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension. Mol Cell Neurosci 2005, 28:779-90). The downstream gene expression changes underlying these pathway-specific responses are largely unknown. The data generated from the proposed project will delineate pathway-specific gene expression responses of astroglia to fibroblast growth factors. This information will allow a rational approach to pharmacological approaches to modulate reactive astrogliosis in brain and spinal cord injury. Determine the astroglial gene expression program elicited by fibroblast growth factor-2, and dissect specific contributions of the ERK and p38 MAP kinase pathways using highly specific pharmacological inhibitors. FGF2, acting via two distinct intracellular signaling pathways, ERK- and p38 MAPK, leads to pathway-specific gene expression changes in astrocytes which promote the morphological plasticity (ERK-dependent) and pro-inflammatory properties (p38-dependent) of reactive astroglia. Cell culture; Neonatal primary astrocyte cultures are prepared exactly as previously described (Heffron and Mandell, 2005), using slight modifications of established protocols (McCarthy and de Vellis, 1980). Astrocytes prepared with these methods comprised greater than 95% of cell cultures as determined by GFAP staining. Microglia are present as a contaminating cell type at a percentage of 3.6 ± 0.9% as determined by CD11B staining. For process induction experiments, cells are trypsinized and replated in DMEM with 1% fetal bovine serum. This low serum concentration is necessary for good adhesion of the cells. Pharmacological inhibitors are dissolved in DMSO and added 2 h later. P38 MAP kinase inhibitors SB202190 (Calbiochem) and the MEK inhibitor U0126 (Promega) are used at 20 µM. We previously determined that the inactive analog of SB 202190, SB202474 (Calbiochem) had no effects on pathway activation or astrocyte morphology. Therefore, the inactive drug analog will not be used in the array experiments. Final DMSO concentration in the drug treatments and vehicle controls is 0.2%. Human recombinant FGF2 (obtained from the National Cancer Institute Preclinical Repository) is used at 25 ng/ml, based on extensive dose/response analyses in our published work.
2008-06-15 | E-GEOD-6675 | biostudies-arrayexpress
Project description:Previous studies indicated that activation of glial cells and inflammatory responses are triggering factors of glaucomatous optic neuropathy. In particular, neurotoxic reactive astrocytes have been found to play a significant role in retinal ganglion cell damage. Furthermore, research showed that activation of glial cells is not dependent on retinal ganglion cell injury, but rather a direct response to pathological elevation of intraocular pressure. However, the molecular mechanism by which elevated intraocular pressure triggers glial activation through mechanical forces remains unknown. By spatial transcriptome sequencing, our study revealed that the neurotoxic astrocyte would rapidly be reactivated in the optic nerve head under elevated intraocular pressure in vivo.
2024-08-31 | GSE241192 | GEO
Project description:Bulk RNA-sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy, in which aspects of AD-related pathology progress at different speed, shows age-dependent gene expression changes. However, bulk RNA-seq does not provide insight into the heterogeneity of expression within this cell type, particularly relevant for such models, where reactive astrogliosis is most prominent in the vicinity of plaques. To investigate astrocyte heterogeneity in ß-amyloidopathy models, we thus performed single cell RNA-sequencing on astrocytes separated by FACS.
2024-03-21 | E-MTAB-13937 | biostudies-arrayexpress
Project description:Reactive gliosis is a complex process that involves profound changes in gene expression. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of reactive gliosis in optic nerve head in response to optic nerve crush injury.
2013-07-15 | GSE40857 | GEO