RNA sequencing of Dorsal Root Ganglia upon axonal injury, in presence or absence of NAC (N-acetyl cysteine), and upon H2O2 nerve treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97090 | GEO | 2018/07/06
REPOSITORIES: GEO
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Project description:Purpose: A) compare the response to an axonal injury in the peripheral vs central nervous system B) clarify the role of HDAC3 in axonal regeneration Results: we found that after peripheral axonal injury there is a higher number of differentially expressed genes regulated by HDAC3 with respect to central injury with a number of genes associated with regenerative pathways
2018-10-01 | GSE104977 | GEO
Project description:Purpose: compare the epigenetic response of DRG neurons to an axonal injury in the peripheral vs central nervous system by measuring accessible chromatin and several histone marks Results: we found that after peripheral axonal injury there is a much greater number of epigenetic changes than after central spinal injury, and that these epigenetic changes after peripheral axotomy tended toward increased chromatin accessibility.
2019-06-19 | GSE108806 | GEO
Project description:The peripheral nervous system (PNS) regenerates after injury. However regeneration is often compromised in case of large lesions, the speed of axon reconnection to their target being critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here, we identify an early response to injury controlled by histone deacetylase (HDAC)2, which coordinates the action of other chromatin-remodeling enzymes to induce the upregulation of Oct6, a key transcription factor for Schwann cell development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion.
2018-10-17 | PXD005383 | Pride
Project description:Retrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate ~900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and ~4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified ~400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response Microarrays were run on mRNA extracted from adult rat L4 and L5 DRGs cells after 1,3,8,12,16,18,24, and 28 hours after a sciatic nerve (proximal and distal) lesion.
2010-12-29 | E-GEOD-26350 | biostudies-arrayexpress
Project description:Methacryloxylethyl cetyl ammonium chloride (DMAE-CB) is a polymerizable antibacterial monomer and has been proved as an effective strategy to achieve bioactive bonding with reliable bacterial inhibitory effects. However, the toxicity of DMAE-CB may hamper its wide application in clinical situations. Thus, this study was designed to investigate the toxicity of DMAE-CB and explore the possible protective effects of N-acetyl cysteine (NAC). High performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analysis showed that chemical binding of NAC and DMAE-CB occurred in a time dependent manner. Pre-incubation of fourty-eight hours is required for adequate reaction between DMAE-CB and NAC. DMAE-CB reduced human dental pulp cells (hDPCs) viability in a dose-dependent manner. The toxic effects of DMAE-CB were accompanied by increased reactive oxygen species (ROS) level and reduced glutathione (GSH) content. NAC alleviated DMAE-CB-induced oxidative stress. Annexin V/ Propidium Iodide (PI) staining and Hoechst 33342 staining indicated that DMAE-CB induced apoptosis. Collapsed mitochondrial membrane potential (MMP) and activation of caspase-3 were also observed after DMAE-CB treatment. NAC rescued hDPCs from DMAE-CB-induced apoptosis, accompanied by lower level of MMP loss and caspase-3 activity. This study assists to elucidate the mechanism underlying the cytotoxic effects of DMAE-CB and provides theoretical supports for the searching of effective strategies to reduce toxicity of quaternary ammonium dental monomers.
| S-EPMC4537128 | biostudies-literature
Project description:In contrast to CNS neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated, along with increased 5-hydroxymethylcytosine (5-hmC) in DRG neurons. We generated genome-wide 5-hmC maps in adult DRG, which demonstrated that peripheral and central axotomy (no regenerative effect) triggered differential 5-hmC changes that are associated with distinct signaling pathways. 5-hmC was altered in half of regeneration-associated genes (RAGs), supporting its role for RAG regulation. Our analyses predicted transcription factors HIF-1, STAT and IRF that may collaborate with Tet3 for 5-hmC modifications. Intriguingly, central axotomy lead to widespread 5-hmC modifications with little overlap with peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5-hmC as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
2016-12-09 | GSE85972 | GEO
Project description:Primary somatosensory neurons specialize in transmitting distinct types of sensory information through differences in cell size, myelination, and the expression of various receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that the different somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells from sensory ganglia, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor which is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that the transcription factors induced early after peripheral sensory neuron injury promote their transcriptional and functional metamorphosis, analogous to their known roles in reprogramming cell fate.
2020-07-22 | GSE154659 | GEO
Project description:Nerve injury in the peripheral nervous system allows spontaneous regeneration, in contrast to injury of central nerves, which lead to a differential expression pattern of regeneration-associated genes and others. These genes might be regulated by promoter DNA methylation As regeneration model, DRG tissue was analyzed for methyated gene promoters and CpG islands following both injury types. A differential methylation pattern could be identified, although most genes remained unmethylated. comparison of DRG following either sciatic nerve axotomy (SNA) or dorsal column axotomy (DCA) - each 'real injury or sham' - at 1, 3 or 7 days post-injury vs. 'naive', Each sample was pooled from two mice, yielding an immunoprecipitated sample ('Test') and an input genomic DNA sample (Ref). altogether 33 microarrays were used for 13 conditions with triplicate arrays for 'real injury' or 'naive' samples, and duplicate arrays for 'sham' samples.
2014-03-05 | E-GEOD-55514 | biostudies-arrayexpress
Project description:After an injury in the adult mammalian central nervous system, lesioned axons fail to regenerate. This failure to regenerate contrasts with the remarkable potential of axons to grow following an injury in the peripheral nervous system. Peripheral sensory neurons with cell soma in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Decades of research have focused on the signaling pathways elicited by injury in sensory neurons and in Schwann cells that insulate axons as central mechanisms regulating nerve repair. However, neuronal microenvironment is far more complex and is composed of multiple cell types including endothelial, immune and glial cells. Whether the microenvironment surrounding neuronal soma contribute to the poor regenerative outcomes following central injuries remains largely unexplored. To answer this question, we performed a single cell transcriptional profiling of the DRG neuronal microenvironment response to peripheral and central injuries. In dissecting the roles of the microenvironment contribution, we have focused on a poorly studied glia population of Satellite Glial Cells (SGC) surrounding the neuronal cell soma. Upon a peripheral injury, SGC contribute to axon regeneration via Fatty acid synthase (Fasn)-PPARα signaling pathway. Our analysis reveals that in response to central injuries, SGC do not activate the PPAR signaling pathway. However, induction of this pathway with fenofibrate, an FDA- approved PPARα agonist used for dyslipidemia treatment, rescued axon regeneration following an injury to the central nerves. Collectively, our results uncovered a previously unappreciated role of the neuronal microenvironment differential response in central and peripheral injuries.
2021-09-12 | GSE158892 | GEO
Project description:Among the vertebrates, teleost and urodele amphibians are capable of regenerating their central nervous system. We have used crush injury method on zebrafish spinal cord, which is a common mammalian mode of injury in spinal cord. To identify the molecular mechanisms of the underlying cellular events during regeneration of zebrafish spinal cord, we have employed high density oligonucleotide microarrays and profiled the temporal transcriptome dynamics during the entire phenomenon. A total of 3842 genes expressed differentially with significant fold changes during spinal cord regeneration. Cluster analysis revealed event specific dynamic expression of genes related to inflammation, cell death, cell migration, cell proliferation, neurogenesis, neural patterning and axonal regrowth. We have also validated the expression pattern of 14 genes (which include inflammatory regulators, cell cycle regulators, pattern forming genes and signaling molecules) by different methodologies. Spatio-temporal analysis of STAT3 expression suggested its possible function in controlling inflammation and cell proliferation. Genes involved in the proliferating neural progenitors and their dorso-ventral patterning (sox2 and dbx2) are differentially expressed. Injury induced cell proliferation is controlled by many cell cycle regulators and some of them also show their common expression in other regenerating systems like fin, heart and retina. We also reported unusual expression pattern of certain pathway genes like one carbon folate metabolism and N-glycan biosynthesis which have not been reported during regeneration of spinal cord. Genes like stat3, socs3, atf3, mmp9 and sox11, which are known to control peripheral nervous system (PNS) regeneration in mammals, are also upregulated in zebrafish spinal cord injury (SCI) thus creating PNS like environment after injury. Our study provides a comprehensive genetic blue print of diverse cellular response(s) during regeneration of zebrafish spinal cord that could be used to induce successful regeneration in mammals. The spinal cord has been injured by crushing dorso-ventrally for 1 sec with a number 5 Dumont forceps at the level of 15th/16th vertebrae. Later the wound were sealed by placing a suture. Both spinal cord injured and sham operated fish were allowed to regenerate and the progress of regeneration was observed after 1, 3, 7, 10 and 15 days of injury. Zebrafishes were anesthetized deeply for 5 minutes in 0.1% tricaine (MS222; Sigma, USA) and approximately 1mm length of spinal cord both rostrally and caudally from injury epicenter were dissected out from 50-60 fishes in each batch and pooled for RNA extraction.
2012-12-01 | E-GEOD-39295 | biostudies-arrayexpress