Rattus norvegicus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD004150
PROVIDER: PRJNA321531 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Network hyperexcitability is manifested as frequent ictal discharges, often caused by unbalanced neurotransmission. We assessed synaptic changes in the hyperexcitable visual cortex of tetanus neurotoxin-injected mice (TeNT). A proteomics analysis of synaptic content revealed Carboxypeptidase E (CPE) up-regulation following TeNT injection. To quantify CPE effect on vesicle clustering, we used an ultrastructural measure of synaptic activity to investigate functional differences at excitatory and inhibitory synapses. We found homeostatic changes in hyperexcitable networks expressed as an early onset lengthening of active zones at inhibitory synapses followed by spatial reorganization at excitatory synapses. Moreover, inhibition of CPE decreases ictal discharges in vivo. This study reveals a complex landscape of homeostatic changes affecting the synaptic release machinery , differentially at inhibitory and excitatory terminals. We propose a novel homeostatic presynaptic mechanism which may impact release timing rather than synaptic strength.
2021-09-09 | PXD022270 | Pride
Project description:In an RNAseq analysis, we have identified the microRNA hsa-miR-129-5p with high levels in acute wounds (day1 to day7) compared to normal skin. The biological function of this miRNA in human epidermal keratinocytes during wound repair has not been studied. To study the genes regulated by miR-129-5p , we transfected miR-mimics targeting miR-129-5p into human primary epidermal keratinocytes to over-express miR-129-5p expression. We performed a global transcriptome analysis of keratinocytes upon miRNA overexpression using Affymetrix arrays.
2024-08-16 | GSE241040 | GEO
Project description:Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.
2020-12-14 | GSE161540 | GEO
Project description:Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses. After 10 days in culture, dissociated mouse hippocampal neurons in 6-well plates were infected with lentivirus expressing either Flag-Nr4a1 or GFP and incubated for 6 days to allow for transgene expression. Total RNA was then isolated using RNeasy Plus kit (QIAGEN). Samples passing an mRNA quality check proceeded to quantitative analysis on Agilent-026655 4x44 Mouse Microarrays.
2016-01-13 | E-GEOD-76805 | biostudies-arrayexpress
Project description:ADGRB1 contributes to astrocyte-mediated phagocytosis of excitatory synapses
| PRJNA1073438 | ENA
Project description:Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses.
2016-01-13 | GSE76805 | GEO
Project description:The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1M-NM-1,M-BM- is regulated at different levels, including the transcriptional level by the Ets factor ELK3. The molecular mechanisms of this intimate transcriptional connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1M-NM-1. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and QPCR. We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop. ELK3 depletion induced hsa-miR-155-5p expression, and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3M-bM-^@M-^Y-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response.M-BM- This crosstalk could be important in the development of new treatments for a range of pathologies. Examination of ELK3 DNA interactions in HUVEC cells under normal oxygen conditions
2014-12-04 | E-GEOD-60156 | biostudies-arrayexpress
Project description:Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer’s disease (AD). However, the cellular-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse models. Single-nucleus RNA sequencing analysis revealed that EphA4 inhibition specifically decreases a reactive astrocyte subpopulation with enriched complement signaling, which are characteristics associated with synapse elimination by astrocytes in AD. Importantly, astrocytic EphA4 knockout in an AD transgenic mouse model decreases complement tagging on excitatory synapses and excitatory synapses within astrocytes. These findings suggest an important role of EphA4 in the astrocyte-mediated elimination of excitatory synapses in AD and highlight the crucial role of astrocytes in hippocampal synapse maintenance in AD.
2024-12-29 | GSE284797 | GEO
Project description:Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer’s disease (AD). However, the cellular-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse models. Single-nucleus RNA sequencing analysis revealed that EphA4 inhibition specifically decreases a reactive astrocyte subpopulation with enriched complement signaling, which are characteristics associated with synapse elimination by astrocytes in AD. Importantly, astrocytic EphA4 knockout in an AD transgenic mouse model decreases complement tagging on excitatory synapses and excitatory synapses within astrocytes. These findings suggest an important role of EphA4 in the astrocyte-mediated elimination of excitatory synapses in AD and highlight the crucial role of astrocytes in hippocampal synapse maintenance in AD.
2025-01-06 | PXD056771 | Pride
Project description:The autism-associated synaptic-adhesion gene Neuroligin-4 (NLGN4) is poorly conserved evolutionarily, limiting conclusions from Nlgn4 mouse models for human cells. Here, we show that the cellular and subcellular expression of human and murine Neuroligin-4 differ, with human Neuroligin-4 primarily expressed in cerebral cortex and localized to excitatory synapses. Overexpression of NLGN4 in human neurons resulted in an increase in excitatory synapse numbers but a remarkable decrease in synaptic strength. Human neurons carrying the syndromic autism mutation NLGN4-R704C also formed more excitatory synapses but with increased functional synaptic transmission due to a postsynaptic mechanism, while genetic loss of NLGN4 did not significantly affect synapses in the human neurons analyzed. Thus, the NLGN4-R704C mutation represents a change of function mutation. Our work reveals contrasting roles of NLGN4 in human and mouse neurons, suggesting human evolution has impacted even fundamental cell biological processes generally assumed to be highly conserved.
2019-06-27 | GSE131428 | GEO