Kinomic analysis of excitotoxicity in primary neuronal cultures
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PROVIDER: PRJNA1073411 | ENA |
REPOSITORIES: ENA
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Project description:Glutamate excitotoxicity plays a critical role in neurodegeneration by triggering NMDA receptorhyperactivation, leading to elevated synaptic calcium levels and subsequent neuronal cell death. Tobetter understand how glutamateaffects neurons in neurological diseases, we conducted acomprehensive analysis of molecular changes at the transcriptome and kinome levels.Our research used primary cortical cultures from rat embryos to study glutamate excitotoxicity. Non-neuronal cells,like astrocytes, typically enhance neuron tolerance to glutamate excitotoxicity. We useda neuron-rich cultured system and observed that the effects of glutamate on neurons are concentration-dependent. Intermediate doses of glutamate had significant neurotoxic effects, while high and lowdoses resulted in less cell mortality, aligning with previous findings related to calcium influx.Glutamate is known to inhibit protein synthesis in neurons and leads to a rise in cytosolic calcium, a keystep in synapticplasticity and delayed neuronal cell death. Kinome profiling indicated activation of PKAand PKG phosphorylation, essential for synaptic plasticity-related gene expression.
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Project description:The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation, differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal cell cultures.
2009-12-01 | GSE17645 | GEO
Project description:Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are central modulators of cellular stress responses, but knowledge about miRNA–mRNA interactions that determine neuronal outcome during inflammation is limited. Here, we combined unbiased neuron-specific miRNA with mRNA sequencing to assemble the regulatory network that mediates robustness against neuroinflammation. As a critical miRNA-network hub we defined miR-92a. Genetic deletion of miR-92a exacerbated the disease course of mice undergoing experimental autoimmune encephalomyelitis (EAE), whereas miR-92a overexpression protected neurons against excitotoxicity. As a key miR-92a target transcript, we identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) that was suppressed in inflamed neurons in mouse EAE and human MS. Accordingly, Cpeb3 deletion improved neuronal resistance to excitotoxicity and ameliorated EAE. Together, we discovered that the miR-92a–Cpeb3 axis confers neuronal robustness against inflammation and serves as potential target for neuroprotective therapies.
2023-11-06 | GSE224558 | GEO
Project description:We investigated functions of miRNAs at the level of the whole transcriptome of primary neurons. We transfected mouse E17.5 forebrain primary neuronal cultures (at four to six days of in vitro development) with miRNA mimics and inhibitors. After approximately 48 h post transfection we profiled the effect of these transfections on gene expression with Illumina mRNA microarrays. Cultures were transfected with mimics and inhibitors of five mouse miRNAs (mmu-miR-124, mmu-miR-434-3p, mmu-miR-143, mmu-miR-145 and mmu-miR-25) and with a mimic of a non-mouse miRNA (cel-miR-67). Direct widespread inhibition of gene expression by the perturbed miRNAs was evident when gene expression in cultures transfected with miRNA mimics was compared to those transfected with the inhibitors (or to matched mock transfected cultures): 3-prime UTRs of downregulated transcripts were significantly enriched in seed matching sites for the perturbed miRNAs. Interestingly, analysis of differential gene expression in mock transfected cells (identified through comparison of mock transfected cultures with matched untreated cultures) revealed that genes inhibited by miRNAs were enriched in genes upregulated in mock transfected cultures. This inhibition was the most efficient by the two neuronal miRNAs under investigation (mmu-miR-124 and mmu-miR-434-3p). To investigate if miRNA mediated inhibition of stress induced genes (i.e. stress associated with transfections) was also the case in other stresses, we profiled gene expression changes triggered by chronic neuronal depolarisation. For this, we treated the cultures with KCl (15 mM, 48 h) and compared them to matched untreated cultures. We found that genes upregulated by KCl had a significant intersection with those upregulated by the mock transfection. Moreover, we also found that genes upregulated by KCl had a significant intersection with genes inhibited by mmu-miR-124 and mmu-miR-434-3p. Therefore we concluded that neuronal miRNAs stabilise the neuronal transcriptome by inhibiting stress inducible genes.
2011-12-31 | E-MTAB-686 | biostudies-arrayexpress
Project description:The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation, differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal cell cultures. Experiment Overall Design: Primary neuronal cell cultures were established from human brain tissue, which was obtained from 8-12 weeks old fetuses at legal abortion after informed consent from the patients. Procedures were approved by the local Ethics committee at the Karolinska University Hospital, Stockholm. A total of 28 tissue samples yielding 10 cell cultures were used in this experiment. Half of the cell cultures were treated with 2µM β-oestradiol the day after seeding. The duration of the oestrogen treatment was 7 days and the cells were harvested after 8 days of culturing for RNA extraction. Extracted RNA from untreated respectively oestrogen treated cell cultures were pooled yielding two samples, which were each hybridised to Affymetrix microarrys.
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