Development of gene expression signatures for BV-2 microglia activation in the background of mild hypothermia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE171696 | GEO | 2021/11/10
REPOSITORIES: GEO
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Project description:Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32°C) or normothermia (37°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.
2014-03-01 | GSE54229 | GEO
Project description:Development of gene expression signatures for BV-2 microglia activation in the background of mild hypothermia
| PRJNA720614 | ENA
Project description:Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32°C) or normothermia (37°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia. Hypothermia was compared against normothermia at seven different time-points. Hypothermic and normothermic mouse embryonic fibroblasts (MEF, in 100 mm dishes, one array per time-point) were submitted to gene expression analysis using Mouse Gene 1.0 ST GeneChip® (Affymetrix) microarrays. Differential gene expression analysis was performed with R package DEMI (http://biit.cs.ut.ee/demi/).
2014-03-01 | E-GEOD-54229 | biostudies-arrayexpress
Project description:Diagnosis of fatal hypothermia is considered to be difficult in forensic practice. In this study, in order to identify novel molecular markers of fatal hypothermia, we made rat models of mild, moderate and severe hypothermia, and performed body temperature-dependent gene expression analysis in illiopsoas muscle using next-generation sequencing.
2019-01-11 | GSE109148 | GEO
Project description:Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE. The aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment.
2023-11-30 | GSE247222 | GEO
Project description:The only validated treatment to prevent brain damage associated with hypoxia-ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective drug candidates include sildenafil citrate, a phosphodiesterase-type 5 inhibitor. The main objective of this preclinical study is to assess its ability to reduce HI-induced neuroinflammation, in particular through its potential effect on microglial activation. HI was induced in P10 Sprague–Dawley rats by unilateral carotid permanent artery occlusion and hypoxia (HI), and treated by either hypothermia (HT) alone, Sildenafil (Sild) alone or combined treatment (SildHT). Lesion size, glial activation were analyzed by immunohistochemistry, qRT-PCR and proteomic analyses performed at P13. Exposure to any treatment was not associated with significant reduction in lesions size both in cerebral cortex and hippocampus, 72h after HI. Significant reductions in either Iba1+ (within the ipsilateral hemisphere) or GFAP+ cells (within the ipsilateral hippocampus) were observed in SildHT group, but not in the other treatment groups. In microglia sorted cells, pro-inflammatory markers, ie. Il1b, Il6, Nos2, and CD86 were significantly downregulated in SildHT treatment group only. These changes were restricted to ipsilateral hemisphere, were not evidenced in sorted astrocytes, and were not sex-dependent. Proteomic analyses in sorted microglia refined the pro-inflammatory effect of HI and confirmed a biologically relevant impact of SildHT on specific molecular pathways including notably genes related to neutrophilic functions. Our findings demonstrate that Sildenafil combined with controlled hypothermia confers maximum effect to mitigate microglial activation induced by HI through complex proteomic regulation. The reduction of neuroinflammation induced by Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.
2024-04-30 | PXD045168 | Pride
Project description:Hypothermia affects the body in positive and negative consequences. In cardiac, hypothermia depresses myocardial contraction, slows conduction, and decreases metabolic rate. However, little is known about the molecular mechanism. Here we compare the genes expression of human adult ventricular cardiomyocyte cells (AC16) treated with hypothermia, trying to find changes under different temperatures and then elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology enrichment analysis revealed that genes related to gene transcriptions, protein and lipid metabolic were significantly enriched. KEGG analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in response to hypothermia. A set of TFs (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. These identified DEGs, pathways and predicted TF could facilitate further investigations of the detailed molecular mechanisms, making it possible to take advantage of the potential applications of hypothermia in broader ranger
2015-07-28 | GSE71361 | GEO
Project description:Hypothermia affects the body in positive and negative consequences. In cardiac, hypothermia depresses myocardial contraction, slows conduction, and decreases metabolic rate. However, little is known about the molecular mechanism. Here we compare the genes expression of human adult ventricular cardiomyocyte cells (AC16) treated with hypothermia, trying to find changes under different temperatures and then elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology enrichment analysis revealed that genes related to gene transcriptions, protein and lipid metabolic were significantly enriched. KEGG analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in response to hypothermia. A set of TFs (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. These identified DEGs, pathways and predicted TF could facilitate further investigations of the detailed molecular mechanisms, making it possible to take advantage of the potential applications of hypothermia in broader ranger AC16 cell lines was treated by hypothermia (n=3) and control group (n=3) for 6 hours.
2015-07-28 | E-GEOD-71361 | biostudies-arrayexpress
Project description:GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If GFRAL+ neurons acutely regulate glucose and energy homeostasis is however underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, or energy fluxes. Our findings reveal that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
2024-03-21 | GSE255540 | GEO
Project description:Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Numerous clinical trials confirmed safety and efficacy of Treg treatment of for deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. In our experiment we demonstrate that mild hypothermia of 33C induces robust proliferation of human Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33C showed stronger immunosuppressive potential and anti-inflammatory phenotype. We show that a simple change in temperature can preserve Treg stability, function and accelerate their proliferation in vitro.
2017-10-04 | E-MTAB-5322 | biostudies-arrayexpress