Smart-seq2 of spinal cord motor neurons reveals transcriptomic changes in mice with spinal cord injury after synergistic bidirectional electrical stimulation of specific frequencies
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PROVIDER: PRJNA924327 | ENA |
REPOSITORIES: ENA
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Project description:Electrical stimulation can augment or modify neuronal function and can have therapeutic benefits for certain neurological disorders. There is evidence that enhancing spinal excitability with either epidural or transcutaneous stimulation can restore some volitional motor output after spinal cord injury (SCI). Lumbosacral epidural stimulation temporarily improves locomotor and autonomic function in both rodents and humans with SCI. When combined with overground locomotor training enabled by a weight-supporting device, epidural electrical stimulation (EES) promotes extensive reorganization of residual neural pathways that improves locomotion after stopping stimulation. However, the exact mechanism underlying the reconstruction of spinal cord neural circuits with electrical stimulation is not yet known. Thus, we developed a epidural electrical and muscle stimulation(EEMS) system at the interface of the spinal cord and muscle to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. Using methods of motor function evaluation, neural circuit tracing and neural signal recording, we discovered a unique stimulus frequency of 10-20 Hz under EEMS conditions that was required for structural and functional reconstruction of spinal sensorimotor circuits. Single-cell transcriptome analysis of EEMS activated motoneurons characterized molecular networks involved in spinal sensorimotor circuit reconstruction. This study provides insights into neural signal decoding during spinal sensorimotor circuit reconstruction, and indicates a technological approach for the clinical treatment of SCI.
2023-12-05 | GSE243038 | GEO
Project description:The characteristics of electrical signals-mediated neural circuits reconstruction remain poorly understood. We initially developed a spinal-muscle synergistic bidirectional electrical stimulation (SBES) protocol to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. The results indicate that sensorimotor circuits could be precisely reassembled in structure and function levels by 10-20 Hz SBES. To gain mechanistic insights into the reassembly of the spinal sensorimotor circuits with 10-20 Hz SBES, we performed gene expression profiling analysis in motoneurons. Gene ontology (GO) analysis showed that one group of GO terms accounted for a large fraction of the upregulated transcripts. This group includes axon growth-related cellular functions, such as cell adhesion, regulation of cell growth, and cell projection assembly. Statistical analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed sixteen signaling pathways were involved, two of which were related to the regulation of axonal regeneration (PI3K-Akt signaling pathway and cAMP signaling pathway). This study provides insights into neural signal decoding during spinal sensorimotor circuit reconstruction.
2024-01-15 | GSE222978 | GEO
Project description:Smart-seq2 of spinal cord motoneurons in spinal cord injury model after dual electrical stimulation with specific frequencies
| PRJNA1016263 | ENA
Project description:To investigate the mechanism of electrical stimulation in the repair of spinal cord injury, we established a rat model of spinal cord injury. Then, we used RNA-SEQ data obtained from ES treatment and 6 different rat models of spinal cord injury for gene expression profile analysis.
2023-07-01 | GSE214291 | GEO
Project description:Electrical stimulation to repair spinal cord injury
| PRJNA989738 | ENA
Project description:The goal of this study is to elucidate the influence of hemisection injury at thoracic spinal cord (T9) and epidural electrical spinal stimulation (L2-S1) on transcriptome of injured thoracic spinal cord. mRNA profiles of spinal cord at 5 days-post injury with or without epidural electrical spinal stimulation (L2-S1) and before injury were generated. Our study represents the detailed analysis of transcriptomes of injured spinal cord with biologic replicates, generated by RNA-seq technology.
2020-05-11 | GSE138637 | GEO
Project description:Purpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload. Methods: Electrical stimulation of the soleus and plantaris muscle was stimulated in female rats with complete transection of the spinal cord at the interspace between the 9th and 10th thoracic vertebrae. Stimulation was begun 16 weeks after spinal cord transection and produced near-isometric contraction of soleus, plantaris and tibialis anterior. Muscle was analyzed at 1, 2 and 7 days after starting exercise with electrical stimulation. To provide a baseline reference for gene expression at 16 weeks after spinal cord injury, muscle was also analysed from an additional group of spinal cord transected animals. One additional group of animals with a sham-spinal cord injury was included to provide information about gene expression in neurologically intact animals of similar age. In parallel studies, rats underwent bilateral gastrocnemius ablation to overload soleus and plantaris, or a sham ablation as a control. Muscle was analyzed at 1, 3 and 7 days after gastrocnemius ablation or sham-ablation. Gene expression was determined using Affymetrix Rat Exon microarrays. For each group of animals, microarray analysis was performed for soleus muscle for each of 3 separate animals, using one array per animal. Control sammples for the spinal cord injured groups included a group of animals with a Sham-spinal cord injury, and a group of spinal cord injured animals that did not get electrical stimulation. The comparator for determining fold-change expression values was the spinal cord injured group that did not receive electrical stimulation. For each day after gastrocnemius ablation, a control was included that received all procedures needed for this ablation except cutting the distal insertion of the gastrocnemius into the Achilles tendon to control for effects of the surgery on gene expression.
2013-03-30 | E-GEOD-37476 | biostudies-arrayexpress
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.
2021-02-16 | GSE155610 | GEO
Project description:Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, which shows that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene, Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis after spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals. Spinal cord injury or control sham injury was performed on adult zebrafish. After 4, 12, or 264 hrs, a 5 mm segment of spinal cord was dissected and processed (as a pool from 5 animals) in three replicate groups for each time point and treatment.
2010-10-19 | E-GEOD-20460 | biostudies-arrayexpress