Identification of genes expressed by spinal cord neurons after axotomy and during axon regeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE2925 | GEO | 2017/12/10
SECONDARY ACCESSION(S): PRJNA92617
REPOSITORIES: GEO
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Project description:Chronic, often intractable pain is caused by neuropathic conditions such as peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations that don’t depend on peripheral axotomy and associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes and long noncoding RNAs. Many transcriptomic changes after SCI were also found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between any rat neuropathic pain model and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural and tissue injury. Although few genes in DRG cells show similar changes in gene expression across all these painful conditions, the few widely shared transcriptional alterations promise novel insights into fundamental mechanisms within DRGs that can drive neuropathic pain.
2022-10-20 | GSE202111 | GEO
Project description:This dataset supports a study investigating the effects of delayed atorvastatin treatment on gene expression and functional recovery in a chronic mouse model of spinal cord injury (SCI). Twelve-week-old female C57BL/6 mice were subjected to moderate 0.25 mm lateral compression SCI and after two weeks, were treated with atorvastatin (10 mg/kg) or a vehicle control daily for four weeks. Bulk RNA sequencing of spinal cord tissues at six weeks post-injury revealed broad alterations to gene expression due to SCI (DEGs common to both treatments and unique to each) and a smaller set of alterations due uniquely to atorvastatin treatment. Atorvastatin treatment specifically activated gene programs associated with axon guidance and fatty acid transport, which may contribute to the enhanced sensorimotor recovery. This RNA-seq dataset offers insights into the molecular underpinnings by which atorvastatin enhances sensorimotor recovery and modulates gene expression post-SCI.
2025-01-05 | GSE271662 | GEO
Project description:To comprehensively elucidate metabolite changes in different anatomical structures (e.g., gray matter and white matter) after spinal cord injury(SCI), our study utilized air-flow-assisted desorption electrospray ionization mass spectrometry imaging platforms to perform untargeted metabolomic studies. These analyzes are designed to identify metabolites critical in spinal cord injury. confirmed the profile differences in white and gray matter as well as in ventral and dorsal horns after SCI. These results provide valuable information for understanding in situ metabolite alterations after SCI.
2025-03-28 | PXD060179 | Pride
Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECMproteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) inDNSCMwere identified as contributors tothese abilities. Furthermore,DNSCMdemonstrated superior performance as a delivery vehicle forNPCs and organoids in spinal cord injury (SCI)models. This suggests that ECMcues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.
2024-03-01 | GSE242908 | GEO
Project description:Although axon regeneration can now be induced experimentally across anatomically complete spinal cord injury (SCI), restoring meaningful function after such injuries has been elusive. This failure contrasts with the spontaneous, naturally occuring repair that restores walking after severe but incomplete SCI. Here, we applied projection-specific and comparative single-nucleus RNA sequencing to uncover the transcriptional phenotype and connectome of neuronal subpopulations involved in natural spinal cord repair. We identified a molecularly defined population of excitatory projection neurons in the thoracic spinal cord that extend axons to the lumbar spinal cord where walking execution centers reside. We show that regrowing axons from these specific neurons across anatomically complete SCI and guiding them to reconnect with their appropriate target region in the lumbar spinal cord restores walking in mice. These results demonstrate that mechanism-based repair strategies that recapitulate the natural topology of molecularly defined neuronal subpopulations can restore neurological functions. Expanding this principle to different classes of neurons across the central nervous system may unlock the framework to achieve complete repair of the injured spinal cord.
2023-09-20 | GSE198949 | GEO
Project description:Spinal cord injury (SCI) is a devastating condition resulting in permanent and irreversible deficits. Despite regeneration attempts, the neurons fail due to several dysfunctions. A number of studies have already revealed that, following SCI, microRNAs show two opposite kinds of alterations, one detrimental and one protective. However, there is still little evidence of specific microRNAs involved in axon regrowth. The aim of this project is the characterization of microRNA expression changes in sensorimotor cortex and corticospinal motor neurons, whose axons are severed by SCI.
2021-08-13 | GSE90452 | GEO
Project description:Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, which finally affects axon regeneration and motor functional recovery. Myofibroblasts have been regarded as the main cell types that filled in the fibrotic scar, however, the cell source of myofibroblasts in transection and crush SCI model remain to be elusive. Here we used lineage tracing or single cell transcription sequencing to investigate the cell origin of fibrotic scar. We found fibrotic scars were filled from PDGFRβ+ daughter cells in spinal cord in crush SCI or transection SCI. The parenchyma perivascular-derived and meninges-derived PDGFRβ+ fibroblasts, but not PDGFRβ+ pericytes, proliferated and contributed to fibrotic cells in the lesion core. The percentage of meninges-derived fibroblasts specifically was higher than parenchyma perivascular-derived fibroblasts in transection model, which might contribute to the more fibrotic scar in transection model than crush model. These findings may provide theoretical support for the treatment of spinal cord injury.
2024-06-07 | GSE218584 | GEO
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9. Keywords: other
2005-02-11 | GSE2270 | GEO
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623
2016-03-30 | GSE76097 | GEO
Project description:The goal of this study was to compare the transcriptional effects of sciatic nerve injury and spinal cord injury on lumbar dorsal root ganglion (DRG) and FACS-sorted dorsal column (DC) sensory neurons. We performed RNA-seq of whole DRG from naïve and spinal cord-injured (SCI) mice (1dpi) and compared this with previously published data for sciatic nerve transection. In order to assess changes specifically in DC neurons, we performed RNA-seq from FACS-sorted DC neurons from Thy1-YFP16 transgenic mice in naïve, sciatic nerve injured (SNI), and SCI (1 and 3dpi). We found that DC neurons alter their transcriptome after SCI, but that gene changes after SCI mostly differ from SNI. These transcriptional differences may reflect both growth promoting and growth inhibitory effects on axon regeneration after SCI.
2021-01-19 | GSE149646 | GEO