Genome wide gene expression analysis of acutely injured primary mouse neurons
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PROVIDER: PRJNA436989 | ENA |
REPOSITORIES: ENA
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Project description:We aimed at identifying a common transcriptional response of neurons to acute injury by conducting a RNA-Seq analysis on primary mouse neurons. We performed parallel damaging of cultured neurons by applying oxygen-glucose deprivation (OGD) as model for cerebral ischemia as well as excitotoxicity induced by the glutamate receptor agonist kainic acid (KA) as an in vitro model amyotrophic lateral sclerosis and epilepsy. For each of the assays, we determined the experimental conditions in which 20% of the cultured cells died due to an 8-hour treatment. In suggesting a convergence of insult-specific upstream factors on shared downstream signals, we assessed the intersection of the conditions and identified 318 statistically significant transcripts with similar regulation in the two in vitro assays
2020-01-13 | GSE111434 | GEO
Project description:Characterization of myocardial B cells in naïve hearts, acutely injured hearts and acutely injured hearts of mice treated with Pirfenidone
| PRJNA449679 | ENA
Project description:Background Transforming growth factor β1 (TGF-β1) has a neuroprotective function in traumatic brain injury (TBI) through its anti-inflammatory and immunomodulatory properties. In our previous study, we found that TGF-β1 played a critical role in inhibiting apoptosis and increasing neuronal activity in murine cortical neurons following trauma. However, the precise mechanisms underlying the neuroprotective actions of TGF-β1 on the cortex require further investigation. Methods Thus, in this study, we were aimed to investigate the regulatory function of TGF-β1 on neuronal autophagy and apoptosis using an in vitro primary cortical neuron trauma-injury model. Results To establish the landscape of differentially expressed genes (DEGs) with or without TGF-β1 (10ng/ml) treatment for 24 hours, we performed RNA-sequencing. We observed significant enrichment of DEGs related to autophagy, apoptosis, and the lysosome pathway in trauma-injured cortical neurons. Additionally, transmission electron microscopy (TEM) confirmed the presence of autophagosomes as well as autophagolysosomes. Western blot analysis revealed upregulation of autophagy-related protein light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, sequestosome 1 (SQSTM1)/p62, along with apoptosis-related protein Cleaved-caspase3 in trauma-injured primary cortical neurons. Furthermore, mechanically injured neurons showed an upregulation of lysosomal marker protein lysosomal marker protein (LAMP1) and lysosomal enzyme mature cathepsin D (mCTSD), but a decrease in the activity of CTSD enzyme. These results indicated that apoptosis was up-regulated in mechanically injured neurons at 24 hours, accompanied by lysosomal dysfunction and impaired autophagic flux. Notably, TGF-β1 significantly reversed these changes. Conclusions Therefore, our findings suggested that TGF-β1 exerted neuroprotective effects on mechanically injured neurons by reducing lysosomal dysfunction, decreasing the accumulation of autophagosomes and autophagolysosomes, and enhancing autophagic flux.
2024-05-10 | GSE249554 | GEO
Project description:Dopamine acts on neurons in the arcuate nucleus of the hypothalamus (ARC) which control homeostatic feeding responses. Here we demonstrate a differential enrichment of Drd1 expression in food intake-promoting AgRP/NPY neurons and a large proportion of Drd2-expressing anorexigenic POMC neurons. This translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine-inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal, that dopamine-mediated POMC neuron inhibition is Drd2-dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators, which manifests in enhanced somatostatin responsiveness of these neurons compared to the global POMC neuron population. Retrograde pseudorabies mapping reveals predominant synaptic input onto these cells from within the ARC as well as characterized dopaminergic cell groups within the hypothalamus and subthalamic areas. Finally, selective chemogenetic activation of POMCDrd2+ neurons uncovers their ability to acutely suppress feeding and to preserve body temperature. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids to our understanding of dopamine-dependent control of homeostatic energy regulatory neurocircuits.
2022-11-08 | GSE210311 | GEO
Project description:Injury of descending motor tracts remodels cortical circuitry and leads to enhanced neuronal excitability, thus influencing recovery following injury. The neuron-specific contributions remain unclear due to the complex cellular composition and connectivity of the CNS. We developed a microfluidics-based in vitro model system to examine intrinsic synaptic remodeling following axon damage. We found that distal axotomy of cultured rat pyramidal neurons caused dendritic spine loss at synapses onto the injured neurons followed by a persistent retrograde enhancement in presynaptic excitability over days. These in vitro results mirrored hyper-activity of directly injured corticospinal neurons in hindlimb motor cortex layer Vb following spinal cord contusion. In vitro axotomy-induced hyper-excitability coincided with elimination of inhibitory presynaptic terminals, including those formed onto dendritic spines. We identified netrin-1 as downregulated following axotomy and exogenous netrin-1 applied 2 days after injury normalized spine density, presynaptic excitability, and the fraction of inhibitory inputs onto injured neurons. These findings demonstrate a novel model system for studying the response of pyramidal circuitry to axotomy and provide new insights of neuron-specific mechanisms that contribute to synaptic remodeling.
2016-11-02 | GSE89407 | GEO
Project description:A phenotypically and functionally distinct population of CD4+ Foxp3+ T cells (Tregs) rapidly accumulates in acutely injured skeletal muscle of mice, just as invading myeloid-lineage cells switch from a pro-inflammatory to a pro-regenerative state. Analysis of gene expression of Tregs and CD4+Foxp3- T cells (Tconvs) from injured muscle and spleen revealed that the transcriptome of muscle Treg cells is distinct from that of splenic Tregs. A set of genes is uniquely expressed by muscle Tregs, while another set is over-expressed by the two muscle populations vis-à-vis their two spleen counterparts. 6 wk-old Foxp3-ires-GFP mice were injured in skeletal muscles with cardiotoxin. Four and fourteen days later, Tregs and Tconvs from spleen and muscle were double-sorted into Trizol. To reduce variability, cells from multiple mice were pooled for sorting, and three replicates were generated for all groups. RNA from 1.5-2.5 x 104 cells was amplified, labeled, and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays.
2013-12-15 | E-GEOD-50096 | biostudies-arrayexpress
Project description:Cell transplantation is a promising approach for reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration and scar formation, as in brain trauma. To elucidate this, we transplanted cells from the embryonic murine cerebral cortex into stab-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative connectomics unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact or inflamed brain, versus exuberant after trauma. In the latter, excessive synapse pruning follows the initial overshoot of connectivity resulting in only a few input connections left. Proteomic profiling identifies candidate molecules involved in the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.
2022-08-12 | PXD023660 | Pride
Project description:Mus musculus strain:primary neurons Genome sequencing
| PRJNA705847 | ENA
Project description:Topo1cc siganls are serving as the marker for the KCl induced acutely enhancer activation in cortical neurons.
2022-08-04 | GSE185649 | GEO
Project description:Ku70/HP1g are serving as the marker for the KCl induced acutely enhancer activation in cortical neurons.
2022-08-04 | GSE185648 | GEO