Global transcriptomic profiling of oxygen-glucose deprivation (OGD)-mediated neuronal injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Minghui Jessica Chen
PROVIDER: E-GEOD-23158 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The present study has used whole-rat genome microarray expression profiling to identify genes whose expression is significantly altered in hippocampal neuronal cultures submitted to oxygen and glucose deprivation (OGD), an established in vitro model for cerebral global ischemia that is suitable for investigations at the molecular level. To do so, total RNA was extracted from hippocampal neuronal cultures at an early (7h) and delayed (24h) time point after OGD, as well as from control neurons. Analysis of gene ontology showed that OGD followed by 7h or 24h of recovery induces changes in the expression levels of genes related with inflammation, response to oxidative stress, metabolism, apoptosis, synaptic proteins and ion channels and, importantly, genes that show different expression levels are mainly specific to one of the two time points of recovery analyzed. The expression levels of several genes were confirmed by qPCR and were in good agreement with the microarray data, showing that the combined use of the OGD model and the microarray technology can be a useful tool for the study molecular mechanisms contributing to the neuronal demise after transient global ischemia. Ischemia induced gene expression in primary hippocampal neuronal rat cultures was measured at 7 and 24 hours after exposure to Oxygen and Glucose deprivation (OGD). Three independent experiments were performed at each time (7 or 24 hours) as independent biological replicates.
2014-06-16 | E-GEOD-54037 | biostudies-arrayexpress
Project description:Oxygen-glucose deprivation (OGD) is a cellular phenomenon consistently observed upon occurrence of ischemic stroke which eventually results in neuronal death. Neuronal cell death after ischemia takes place via two distinct processes, necrosis and apoptosis. Apoptosis, programmed cell death, is denoted by chromatin condensation, nuclear blebbing, cellular shrinkage, and DNA fragmentation. Unlike apoptosis, cellular swelling and lysis is suggestive of necrosis. However, these two processes are related not only to the severity but also to the duration of ischemia.
2013-12-31 | GSE23158 | GEO
Project description:Abstract Background: Cerebral ischemia-reperfusion (I/R) frequently caused the late-onset neuronal damage. Breviscapine has a promote in autophagy of microvascular endothelial cells in I/R and it can inhibit the oxidative damage and apoptosis. However, the mediation mechanism of breviscapine on neuronal cell death is unclear. Methods: Firstly, transcriptome sequencing was performed on three groups of mice neuronal normal group (Control group), oxygen-glucose deprivation/reoxygenation group (OGD/R group) and breviscapine administration group (Therapy group). Differentially expressed genes (DEGs) between OGD/R and Control groups, and between Therapy and OGD/R groups were obtained by limma package. The N6-methyladenosine (m6A) methylation related DEGs were selected out by the Pearson correlation analysis. Then, prediction and confirmation of drug targets were performed by Swiss Target Prediction and UniProt Knowledgebase (UniProtKB) datebase, and key genes were obtained by Pearson correlation analysis between m6A-related DEGs and drug target genes. Next, gene set enrichment (GSEA) analysis and Ingenuity pathway analysis (IPA) were used to obtain the pathways of key genes. Finally, a circRNA-miRNA-mRNA network was constructed based on the mRNAs, circRNAs and miRNAs. Results: 2250 DEGs between OGD/R and Control groups and 757 DEGs between Therapy and OGD/R groups were selected out by differential analysis. A total of 7 m6A related DEGs including Arl4d, Gm10653, Gm1113, Kcns3, Olfml2a, Stk26 and Tfcp2l1 were obtained by Pearson correlation analysis. Four key genes (Tfcp2l1, Kcns3, Olfml2a and Arl4d) were acquired, and GSEA showed that these key genes were significantly participated in DNA repair, e2f targets and g2m checkpoint. IPA revealed that Tfcp2l1 played a significant role in human embryonic stem cell pluripotency. The circRNA-miRNA-mRNA network showed that the mmu_circ_0001258 regulated the Tfcp2l1 by mmu-miR-301b-3p. Conclusions: In conclusion, four key genes including Tfcp2l1, Kcns3, Olfml2a and Arl4d significantly associated with the treatment of OGD/R by breviscapine were acquired, which would provide a theoretical basis for clinical trials.
2024-05-17 | E-MTAB-13017 | biostudies-arrayexpress
Project description:Fibroblasts usually mediate acute wound healing and long-term tissue remodeling with scarring in tissue injury. In myocardial infarction (MI), following a prolonged lack of oxygen supply, necrotized cardiomyocytes become replaced by secreted extracellular matrix proteins produced by fibroblasts. Dendritic cells (DCs) act as inflammatory cells and can migrate from the bone marrow to the infarct areas and infarct border areas to mediate collagen accumulation after MI, whereas trichostatin A (TSA) can regulate the apoptosis and proliferation of the fibroblasts and affect DCs functions under oxygen–glucose deprivation (OGD) conditions. In this study, we used proteomics to investigate the effects of TSA and bone marrow-derived dendritic cells (BMDCs) on NIH3T3 fibroblasts under OGD conditions. Results showed that the fatty acid degradation pathway was significantly upregulated in NIH3T3 cells under OGD conditions, and the fatty acid synthesis pathway was significantly downregulated in NIH3T3 cells treated with BMDCs conditioned media with TSA (BMDCs-CM[TSA]) under OGD conditions. Meanwhile, the BMDCs-CM(TSA) significantly decreased the levels of triglycerides and free fatty acids and mediated ten fatty acid metabolism-related proteins in the NIH3T3 cells under OGD conditions. Summarily, the proteomic analysis showed that TSA and BMDCs affect fatty acid metabolism in NIH3T3 cells under OGD conditions.
2024-05-21 | PXD021469 | Pride
Project description:The human immortalized brain endothelial cell line hCMEC/D3 is considered an in vitro model of the blood-brain-barrier. We aimed to characterize changes in the secretome of hCMEC/D3 subjected to oxygen and glucose deprivation (OGD) by SILAC, in order to identify new proteins involved in ischemia-triggered blood-brain-barrier disruption and test their potential as blood biomarkers for ischemic stroke diagnosis. After SILAC analysis, 19 proteins were found differentially secreted between OGD and normoxia/normoglycemia conditions (Fold Change>|1.4| and peptide count≥2). Protein folding and nucleic acid binding were the main molecular functions and epithelial adherens junctions and aldosterone signaling appeared as the main canonical pathways represented by OGD-secreted proteins. ANXA1, CLUS, IGFBP2, PRDX3, TIMP2 and COL1A2 were replicated by western blotting in 9 independent cell cultures. Five replicated proteins were analyzed in human serum samples of 38 ischemic stroke patients compared to 18 stroke-mimicking conditions and 18 healthy controls by ELISA. IGFBP2 showed increased blood levels when strokes were compared with stroke-mimicking patients (p<0.1). In conclusion, we characterized changes in the secretome of hCMEC/D3 after an ischemic insult and highlighted some candidates to become biomarkers for ischemic stroke diagnosis related to blood-brain-barrier disruption.
2016-01-21 | PXD002292 | Pride
Project description:AMPA receptors are involved not only in neuronal plasticity but also in excitotoxicity, mediated largely by the influx of Ca2+ (Choi et al., 1988). Their implication has been highlighted in animal models of ischemia and epilepsy. Studies of ischemic rodent models featured that prior to cell death, hippocampal CA1 pyramidal cells exhibit an increased AMPA receptor-mediated Ca2+ influx and decreased GluR2 and GluR3 mRNA and protein levels (Gorter et al., 1997; Heuerteaux et al., 1995). A total of 15 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 300uM AMPA over a time-course of 5h, 15h and 24h (n=3) in addition to the vehicle control (n=6).
2013-12-31 | E-GEOD-22993 | biostudies-arrayexpress
Project description:Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Pharmacological proteasomal inhibitors such as lactacystin can induce apoptosis in cultured mouse cortical neurons through the activation of caspase-3. However, Meiners et al., 2003 suggested that low dose of lactacystin induces a concerted expression of proteasome genes and de novo formation of proteasomes. We discovered by microarray analysis that lactacystin treatment induces a dose-dependent biphasic modulation of both potentially neuroprotective as well as pro-apoptotic genes in neurons. Microarray analysis was carried out using 24 Illumina mouse Ref8V1.1 genechip arrays. The assignment of the arrays was as follows: Controls (n=6); exposure to 1 ?M (High) lactacystin for 5h, 8h, 15h and 24 h (n=3 respectively) and 0.1uM (Low) for 15h and 24h (n=3 respectively).
2013-12-31 | E-GEOD-23155 | biostudies-arrayexpress
Project description:The present study has used whole-rat genome microarray expression profiling to identify genes whose expression is significantly altered in hippocampal neuronal cultures submitted to oxygen and glucose deprivation (OGD), an established in vitro model for cerebral global ischemia that is suitable for investigations at the molecular level. To do so, total RNA was extracted from hippocampal neuronal cultures at an early (7h) and delayed (24h) time point after OGD, as well as from control neurons. Analysis of gene ontology showed that OGD followed by 7h or 24h of recovery induces changes in the expression levels of genes related with inflammation, response to oxidative stress, metabolism, apoptosis, synaptic proteins and ion channels and, importantly, genes that show different expression levels are mainly specific to one of the two time points of recovery analyzed. The expression levels of several genes were confirmed by qPCR and were in good agreement with the microarray data, showing that the combined use of the OGD model and the microarray technology can be a useful tool for the study molecular mechanisms contributing to the neuronal demise after transient global ischemia.
2014-06-16 | GSE54037 | GEO
Project description:miRNA microarray profiling of primary cortical neurons exposed to 4h oxygen and glucose deprivation (OGD) in vitro. RNA samples collected at 8h post-OGD terminaion. miRNAs were also profiled in mice exposed to 3- vessel occlusion model of stroke. RNA samples collected from contralateral (control) and ipsilateral (infarct) sides of the brain following 24h of reperfusion. Comparison of control and ischemic samples across 3 biological replicates for both in vitro and in vivo samples. In vitro cultures consisted of primary cortical neurons derived from E17 rat Wistar embryos. In vivo samples were obtained from C57bl/6 mice exposed to three-vessel occlusion.
2013-11-21 | E-GEOD-51586 | biostudies-arrayexpress
Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPM-NM-1/M-NM-2 transcription factors and CTCF, thereby governing intricate control of neuronal development. mRNA and long non-coding RNA expression profiling of maturing primary cortical neurons from E15 mouse embryos and neurons subjected to oxygen-glucose deprivation. Maturing neurons were harvested on Days 2, 4, 6 and 8. Neurons on Day 6 were subjected to oxygen-glucose deprivation for different time periods and 24 hours reperfusion before being harvested.
2014-10-24 | E-GEOD-44833 | biostudies-arrayexpress