Global transcriptomic profiling of oxygen-glucose deprivation (OGD)-mediated neuronal injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23158 | GEO | 2013/12/31
SECONDARY ACCESSION(S): PRJNA131563
REPOSITORIES: GEO
Similar Datasets
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. Microarray analysis was carried out using 20 Illumina mouse Ref8V1.1 genechip arrays. The assignment of the arrays was as follows: Controls (n=5); exposure to OGD for 10min, 5h, 8h, 15h and 24 h (n=3 respectively).
2013-12-31 | E-GEOD-23158 | 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. 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: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: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:To elucidate the mechanism of enarodustat pretreatment-induced protection against oxygen-glucose deprivation (OGD), we have we have employed whole genome microarray expression profiling as a discovery platform to identify genes upregulated by enarodustat exposure. HK2 cells were pretreated with either vehicle (DMSO) or enarodustat for 24 hours prior to OGD for 16 hours. Pathway analysis revealed upregulated glysolysis pathway.
2020-04-14 | GSE130144 | GEO
Project description:Brain microvascular endothelial cell (BMEC) injury can affect neuronal survival by modulating immune responses through the microenvironment. We used microarrays to detail the miRNAs expression in the exosomes from normal and oxygen glucose deprivation (OGD)-cultured BMECs.
2023-03-08 | GSE224961 | GEO
Project description:Oxygen and glucose metabolism plays a pivotal role in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) occurs during ischemia and stroke, resulting in extensive tissue injury and cell death. We applied time-resolved ribosome profiling technique to assess early events at the level of gene expression in rat pheochromocytoma PC12 cells during short-term OGD. Most substantial alterations in transcripts levels and their translation were seen to occur in the first 20 minutes of OGD. The rapid adaptation of translation apparatus to OGD is global and involves altered elongation and initiation rates. We also observed salient and reproducible alterations in ribosome densities of individual mRNAs such as increased translation of particular upstream Open Reading Frames (uORFs); induced site-specific arrests of the ribosomes and synthesis of extended protein isoforms. Ribosome profiling (with mRNA-seq sequencing) was carried out at 0,20,40 and 60 minutes of OGD. Two biological replicates were used.
2015-04-10 | E-GEOD-60752 | biostudies-arrayexpress
Project description:Metabolic stress and the increased production of reactive oxygen species (ROS) are two main contributors to neuronal damage and synaptic plasticity in acute ischemic stroke (AIS). The superoxide scavenger MnTMPyP has been previously reported to have a neuroprotective effect in organotypic hippocampal slices and to modulate synaptic transmission after in vitro hypoxia and oxygen glucose deprivation (OGD). However, the mechanisms involved in the effect of this scavenger remain elusive. In this study we evaluated the concentration dependent effect of MnTMPyP on synaptic transmission during ischemia and post-ischemic synaptic potentiation. We also investigated the complex molecular changes supporting cellular adaptation to metabolic stress and how these are modulated by MnTMPyP. Electrophysiological data showed that MnTMPyP causes a concentration dependent decrease in baseline synaptic transmission and impairment of synaptic potentiation. Proteomic analysis performed on MnTMPyP treated tissue indicated an impairment in vesicular trafficking mechanisms including alteration of Secretory Carrier Membrane Protein 3 (SCAMP3) and RAB proteins and downregulation of mitochondrial-mediated apoptosis. Alterations of vesicular trafficking may lead to reduced probability of neurotransmitter release and AMPA receptor activity, resulting in the observed modulatory effect of MnTMPyP. In ischemia and glucose deprivation, protein enrichment analysis highlighted impairments in cell proliferation and differentiation, such as TGFβ1 and CDKN1B signalling, in addition to downregulation of actin signalling, cell stress and mitochondrial-mediated apoptosis. Taken together our results indicate modulation of neuronal sensitivity to the ischemic insult, and a complex role for MnTMPyP on synaptic transmission and plasticity and provide molecular insights into the mechanisms mediating the effects of MnTMPyP during ischemia
2023-05-10 | PXD040890 | Pride
Project description:Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remains largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. We identified Prmt5 as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. Prmt5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that Prmt5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, we treated mice with middle cerebral artery occlusion (MCAO) with the Prmt5 inhibitor EPZ015666 and found that Prmt5 inhibition sustain protection against neuronal death in vivo. Together, our findings revealed a novel epigenetic mechanism of Prmt5 in cerebral ischemia and uncovered a potential target for neuroprotection.
2024-02-10 | GSE248392 | GEO
Project description:Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remains largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. We identified Prmt5 as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. Prmt5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that Prmt5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, we treated mice with middle cerebral artery occlusion (MCAO) with the Prmt5 inhibitor EPZ015666 and found that Prmt5 inhibition sustain protection against neuronal death in vivo. Together, our findings revealed a novel epigenetic mechanism of Prmt5 in cerebral ischemia and uncovered a potential target for neuroprotection.
2024-02-10 | GSE248390 | GEO