Effect of 15-PGDH inhibition on skeletal muscle after sciatic nerve transection by single nuclei analysis
Ontology highlight
ABSTRACT: There are currently no approved treatments for the weakness and paralysis that result from loss of peripheral nerve function with aging, trauma, or neuromuscular disease. Here we use single nuclei sequencing to show that denervation due to transection of the sciatic nerve triggers a striking increase in the prostaglandin degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle.
Project description:Changes in microRNA (miRNA) expression in the mouse L4 and L5 dorsal root ganglion following unilateral sciatic nerve transection. The timepoint of 7 days post-axotomy was chosen to capture miRNA expression profiles at a time when the injured neurons were beginning to regenerate. Two condition experiment, paired control DRG vs axotomised DRG following unilateral sciatic nerve transection. 3 biological replicates, one replicate per array. Dye swap in Replicate 2.
Project description:The goal of this study was to analyze global gene expression in FACS purified Nav1.8 lineage sensory neurons, which include nociceptor neurons that detect damaging/noxious stimuli, following peripheral inflammation by intraplantar injection of Complete Freund's Adjuvant (CFA) or Sciatic Nerve Injury (SNI) by nerve transection. Nav1.8 Trangsgenic TdTomato+ neurons were purified from Lumbar L4-L6 dorsal root ganglia (DRG) by flow cytometry from mice on the ipsilateral or contralateral sides, following Complete Freund's Adjuvant injection (day 1) or sciatic nerve transection (day 5). Neurons were then analyzed for transcriptional gene expression by microarray analysis.
Project description:Changes in microRNA (miRNA) expression in the mouse L4 and L5 dorsal root ganglion following unilateral sciatic nerve transection. The timepoint of 7 days post-axotomy was chosen to capture miRNA expression profiles at a time when the injured neurons were beginning to regenerate.
Project description:We have performed parallel scRNA-seq and snATAC-seq analysis of skeletal muscles subjected to sciatic nerve transection to delineate cell type-specific patterns of gene expression and chromatin accessibility at different time-points post-denervation. This analysis revealed that, unlike muscle injury, denervation leads to the selective activation of specific muscle-resident cell types, such as glial cells and a population of mesenchymal cells marked by the expression of Thy1/CD90.
Project description:Fast and slow skeletal muscles show different characteristics and phenotypes. This data obtained from microarray includes the comparison of normal fast plantaris and slow soleus muscles of adult rats. Characters of slow muscle are strongly dependent on the level of muscular activity. Denervation silences the muscular activity. Therefore, we determined the effects of denervation on gene expression in slow soleus muscle of adult rats. Denervation was performed by transection (~5 mm) of left sciatic nerve at the gluteal level. No treatments were made in the normal control rats. Sampling of soleus and/or plantaris was performed in both normal and experimental groups 28 days after the surgery.
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular disorder characterized by the selective degeneration of upper and lower motor neurons, progressive muscle wasting and paralysis. To define the full set of alterations in gene expression in skeletal muscle during the course of the disease, we performed high-density oligonucleotide microarray analysis of gene expression in hind limb skeletal muscles of sod1(G86R) mice, one of the existing transgenic models of ALS. To monitor denervation-dependent gene expression, we determined the effects of short-term acute denervation on the muscle transcriptome after sciatic nerve axotomy.
Project description:Analysis of extruded axoplasm proteomes from adult rat sciatic nerves in vivo by Label Free Quantitative Proteomics (LFQ) and comparison of normal and injury (18 hours post complete nerve transection) conditions. A combination of BONCAT and MS/MS were also performed to analyze the top axonal newly synthetized proteins in vivo.
Project description:To compare the microRNAs (miRNAs) expression profile in the innervated soleus muscle and L4-L6 DRG neuronsafter sciatic nerve entrapment with a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury. The experimental soleus muscles and dorsal root ganglions (DRGs) from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed with an Agilent® rat miRNA array to detect dysregulated miRNAs Three-condition experiment, DRGs and soleus muscles of the rats receiving sciatic nerve denervation 6 months, sciatic nerve entrapment 6 months, and sciatic nerve entrapment 6 months then decompression for 3 months v.s. soleus muscle (sham control), Biological replicates: 1 control replicates, 3 experiment replicates
Project description:We reported the gene expression analysis of different types of sensory neuron with peripheral nerve transection treatment on single cell level. We found substantial variation between myelinated large diameter neurons and small diameter nonpeptidergic nociceptors, in both terms of regeneration response genes regulation as well as fraction of cells respond to nerve injury.