Project description:Patients carrying one or two ApoE4 alleles suffer from worse functional recovery after spinal cord injury. Using transgenic mice expression human ApoE3 or ApoE4 we investigated potential cellular mechanisms of reduced recovery after spinal cord injury. Bulk RNA sequencing of the spinal cord lesion site followed by pathway enrichment analysis predicts that ApoE4 mice have a higher inflammatory and extracellular matrix remodeling activity 7 days after spinal cord injury. Contrary, higher activities for neuronal projection and action potential patways were predicted in the ApoE3 mice at 21 days after injury.
Project description:We use transcriptome analysis to study the spinal cord transcriptome during MHV-induced demyelinating disease and find important biological pathways for demyelinating pathology. We find evidence of a Th1 cytokine response, ongoing antigen presentation and lymphocyte proliferation, lipid metabolism changes, and eicosanoid inflammation. In addition, we report several genes important for osteoclast function have augmented expression in the CNS during demyelination, suggesting a parallel between the osteoclast and microglial functions in maintaining homeostasis and the fidelity of specialized extracellular matrices in their respective compartments. RNA-seq of mock-infected and MHV-infected spinal cord tissue at 33 days post-infection, the peak of demyelination.
Project description:After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing to profile how each cell type in the lumbar spinal cord changes after a thoracic injury in mice. We present an atlas of these dynamic responses across dozens of cell types in the acute, subacute, and chronically injured spinal cord. Using this resource, we find rare spinal neurons that express a signature of regeneration in response to injury, including a major population that represent spinocerebellar projection neurons. We characterize these cells anatomically and observed axonal sparing, outgrowth, and remodeling in the spinal cord and cerebellum. Together, this work provides a key resource for studying cellular responses to injury and uncovers the spontaneous plasticity of spinocerebellar neurons, uncovering a potential candidate for targeted therapy.
Project description:Label-free mass spectrometry-based quantitative proteomics was applied to a larval zebrafish spinal cord injury model, which allows axon regeneration and functional recovery within two days (days post lesion; dpl) after a spinal cord transection in 3 day-old larvae (dpf). Proteomic profiling of the lesion site was performed at 1 dpl and 2 dpl as well as corresponding age-matched unlesioned control tissue (4 dpf as control for 1 dpl; 5 dpf as control for 2 dpl).
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. Hypothesis: Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known. Specific Aim: The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy.
Project description:Spinal cord injury disrupts ascending and descending neural signals causing sensory and motor dysfunction below the injury. Neuromodulation with electrical stimulation is used in both clinical and research settings to induce neural plasticity and improve functional recovery following injury. However, the mechanisms by which electrical stimulation affects recovery remain unclear. In this study we examined the effects of cortical electrical stimulation following injury on transcription at several levels of the central nervous system. We performed a unilateral cervical spinal contusion injury in rats and delivered stimulation for one week to the contralesional motor cortex to activate a descending motor tract.RNA was purified from bilateral subcortical white matter, and 3 levels of the spinal cord. Here we provide the complete data set in the hope that it will be useful for researchers studying electrical stimulation as a therapy to improve recovery from the deficits associated with spinal cord injury.
Project description:Here, we show that epidural electrical stimulation (EES) of the lumbar spinal cord applied during neurorehabilitation (EESREHAB) restored walking in nine people with chronic spinal cord injury (SCI). This recovery involved a reduction of the metabolic activity in the lumbar spinal cord during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential to walk after SCI. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing and spatial transcriptomics to the spinal cord of these mice to chart a spatially-resolved molecular atlas of recovery from paralysis. We then employed cell type and spatial prioritization to uncover the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons were not necessary to walk before SCI, we demonstrate that they are essential to regain walking following SCI. In turn, augmenting their activity instantly phenocopied the recovery of walking enabled by EESREHAB. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after SCI. Moreover, our methodology establishes a framework to identify the neurons producing complex behaviours using molecular cartography.
Project description:Here, we show that epidural electrical stimulation (EES) of the lumbar spinal cord applied during neurorehabilitation (EESREHAB) restored walking in nine people with chronic spinal cord injury (SCI). This recovery involved a reduction of the metabolic activity in the lumbar spinal cord during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential to walk after SCI. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing and spatial transcriptomics to the spinal cord of these mice to chart a spatially-resolved molecular atlas of recovery from paralysis. We then employed cell type and spatial prioritization to uncover the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons were not necessary to walk before SCI, we demonstrate that they are essential to regain walking following SCI. In turn, augmenting their activity instantly phenocopied the recovery of walking enabled by EESREHAB. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after SCI. Moreover, our methodology establishes a framework to identify the neurons producing complex behaviours using molecular cartography.
Project description:This project is "Phosphoproteomic analysis of the lumbar spinal cord, a lesion site in the amyotrophic lateral sclerosis (ALS) mouse model SOD1G93A mice". The aim of this study is to clarify the phosphorylation changes by the lumbar spinal cord of SOD1G93A mice at 20w by applying proteomics technology. The goal of this study is to better understand the pathogenesis of ALS. lumbar spinal cord of SOD1G93A mice (n=5) and WT mice (n=4) were collected at 20w, and the phosphoproteomics were compared.