Spinal cord and dorsal root ganglion gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE5425 | GEO | 2006/08/02
SECONDARY ACCESSION(S): PRJNA96085
REPOSITORIES: GEO
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Project description:We used microarrays to test the fundamental quantitative differences between central and peripheral nervous system transcriptomes. Experiment Overall Design: 3 independent SC and 3 independent DRG samples were analyzed. Each sample contained material from 4 age-matched male C57B/6 mice.
2007-11-27 | E-GEOD-5425 | biostudies-arrayexpress
Project description:Glial cells are present throughout the entire nervous system and paly a crucial role in regulating physiological and pathological functions, such as infections, acute injuries and chronic neurodegenerative disorders. The glial cells mainly include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS), and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Although the glial subtypes and functional heterogeneity is relatively well understood in mice by recent studies using single-cell or single-nucleus RNA-sequencing, no evidence yet has elucidate the transcriptomic profiles of glia cells in PNS and CNS. Here, we used high-throughput single-nucleus RNA-sequencing to map the cellular and functional heterogeneity of SGCs in human dorsal root ganglion (DRG), and astrocytes, microglia, and oligodendrocytes in human spinal cord. In addition, we compared the human findings with previous single-nucleus transcriptomic profiles of glial cells from mouse DRG and spinal cord. This work will comprehensively profile glial cells heterogeneity and will provide a powerful resource for probing the cellular basis of human physiological and pathological conditions related to glial cells.
2022-02-24 | GSE189501 | GEO
Project description:The sensory neurons of the dorsal root ganglia (DRG) must project accurately to their central targets to convey proprioceptive, nociceptive and mechanoreceptive information to the spinal cord. How these different sensory modalities and central connectivities are specified and coordinated still remains unclear. Given the expression of the POU homeodomain transcription factors Brn3a/Pou4f1 and Brn3b/Pou4f2 in DRG and spinal cord sensory neurons, we determined the subtype specification of DRG and spinal cord sensory neurons as well as DRG central projections in Brn3a and Brn3b single and double mutant mice. Inactivation of either or both genes causes no gross abnormalities in early spinal cord neurogenesis; however, in Brn3a single and Brn3a;Brn3b double mutant mice, sensory afferent axons from the DRG fail to form normal trajectories in the spinal cord. The TrkA(+) afferents remain outside the dorsal horn and fail to extend into the spinal cord, while the projections of TrkC(+) proprioceptive afferents into the ventral horn are also impaired. Moreover, Brn3a mutant DRGs are defective in sensory neuron specification, as marked by the excessive generation of TrkB(+) and TrkC(+) neurons as well as TrkA(+)/TrkB(+) and TrkA(+)/TrkC(+) double positive cells at early embryonic stages. At later stages in the mutant, TrkB(+), TrkC(+) and parvalbumin(+) neurons diminish while there is a significant increase of CGRP(+) and c-ret(+) neurons. In addition, Brn3a mutant DRGs display a dramatic down-regulation of Runx1 expression, suggesting that the regulation of DRG sensory neuron specification by Brn3a is mediated in part by Runx1. Our results together demonstrate a critical role for Brn3a in generating DRG sensory neuron diversity and regulating sensory afferent projections to the central targets.
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Project description:Cell adhesion molecules belonging to the immunoglobulin superfamily (IgSF) control synaptic specificity through hetero- or homophilic interactions in different regions of the nervous system. In the developing spinal cord, monosynaptic connections of exquisite specificity form between proprioceptive sensory neurons and motor neurons, however, it is not known whether IgSF molecules participate in regulating this process. To determine whether IgSF molecules influence the establishment of synaptic specificity in sensory-motor circuits, we examined the expression of 157 IgSF genes in the developing dorsal root ganglion (DRG) and spinal cord by in situ hybridization assays. We find that many IgSF genes are expressed by sensory and motor neurons in the mouse developing DRG and spinal cord. For instance, Alcam, Mcam, and Ocam are expressed by a subset of motor neurons in the ventral spinal cord. Further analyses show that Ocam is expressed by obturator but not quadriceps motor neurons, suggesting that Ocam may regulate sensory-motor specificity in these sensory-motor reflex arcs. Electrophysiological analysis shows no obvious defects in synaptic specificity of monosynaptic sensory-motor connections involving obturator and quadriceps motor neurons in Ocam mutant mice. Since a subset of Ocam+ motor neurons also express Alcam, Alcam or other functionally redundant IgSF molecules may compensate for Ocam in controlling sensory-motor specificity. Taken together, these results reveal that IgSF molecules are broadly expressed by sensory and motor neurons during development, and that Ocam and other IgSF molecules may have redundant functions in controlling the specificity of sensory-motor circuits.
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Project description:Despite the established efficacy and effectiveness of Spinal Cord Stimulation (SCS), there is still no consensus on the supraspinal mechanisms of action of this therapy. The purpose of this study was to systematically review previously raised hypotheses concerning supraspinal mechanisms of action of SCS based on human, animal and computational studies. Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS and Web of Science), backward reference searching and consultation with experts. The study protocol was registered prior to initiation of the review process (PROSPERO CRD42020161531). A total of 54 publications were included, 21 of which were animal studies, and 33 were human studies. The supraspinal hypotheses (n = 69) identified from the included studies could be categorized into six groups concerning the proposed supraspinal hypothesis, namely descending pathways (n = 24); ascending medial pathway (n = 13); ascending lateral pathway (n = 10); affective/motivational influences (n = 8); spinal-cerebral (thalamic)-loop (n = 3) and miscellaneous (n = 11). Scientific support is provided for the hypotheses identified. Modulation of the descending nociceptive inhibitory pathways, medial and lateral pathways were the most frequently reported hypotheses about the supraspinal mechanisms of action of SCS. These hypotheses were mainly supported by studies with a high or moderate confidence in the body of evidence.
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Project description:BackgroundGlycine receptors (GlyRs) are involved in the development of spinal pain sensitization. The GlyRα3 subunit has recently emerged as a key factor in inflammatory pain pathways in the spinal cord dorsal horn (DH). Our study is to identify the extent of location and cell types expressing different GlyR subunits in spinal cord and dorsal root ganglion (DRGs). To tease out the possible actions of GlyRs on pain transmission, we investigate the effects produced by GlyRs on acute inflammatory pain by behavioral testing using prostaglandin E2 (PGE2) intrathecal injection models. Furthermore, we investigate the changes of GlyR expression in DRGs and spinal cord in rats after the induction of acute inflammatory pain.ResultsCompared to the vehicle administration, the PGE2 intrathecal injection model produced significantly higher hyperalgesia, which started 3 h after PGE2 injection and lasted more than 5 h. PGE2 intrathecal injection significantly decreased GlyRα1 and GlyRα3 protein expressions in the L5 DH at 1 h and lasted to 5 h, and similar results were observed in the L5 DRG at 5 h. Confocal microscopic images showed the co-existence of punctate gephyrin and GlyRα3 immunoreactivity (IR) throughout the gray matter of the spinal cord, mainly in DH laminae I-III neurons and in ventral horn neurons. It also showed the co-existence of punctate gephyrin and GlyRα3 IR in DRG neurons.ConclusionsIn this study, PGE2 intrathecal injection significantly decreased protein expression of gephyrin, GlyRα1 and GlyRα3 in spinal cord DH and DRG. The gephyrin and GlyRα3 were localized on neuron cells both in the DH and DRG.
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Project description:Leptin (Lep) is mainly, although not exclusively, secreted by adipocytes. In addition to regulating lipid metabolism, it is also a proinflammatory factor and involved in the development of neuropathic pain after peripheral nerve injuries (PNI) (Lim et al., 2009; Maeda et al., 2009) [1,2]. Leptin or its messenger ribonucleic acid expression has been found in various brain regions normally and in the dorsal horn after PNI (Lim et al., 2009; Ur et al., 2002; La Cava et al., 2004; White et al., 2004) [1,[3], [4], [5]]. However, the expression pattern of Lep and Leptin receptor (LepR) after preganglionic cervical root avulsion (PCRA) is still unknown. We provide data in this article related to Chang et al. (2017) [6]. Here, our data showed a profound Lep and LepR expression in the neurons of dorsal root ganglion (DRG) after PCRA. Moreover, the expression of Lep and LepR were also identified in significant portions of the neurons and microglia located in the dorsal horn. The roles of these increased expressions in the development of neuropathic pain after PCRA deserve further study.
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Project description:Understanding molecular alterations associated with peripheral inflammation is a critical factor in selectively controlling acute and persistent pain. The present report employs in situ hybridization of the 2 opioid precursor mRNAs coupled with quantitative measurements of 2 peptides derived from the prodynorphin and proenkephalin precursor proteins: dynorphin A 1-8 and [Met5]-enkephalin-Arg6-Gly7-Leu8. In dorsal spinal cord ipsilateral to the inflammation, dynorphin A 1-8 was elevated after inflammation, and persisted as long as the inflammation was sustained. Qualitative identification by high performance liquid chromatography and gel permeation chromatography revealed the major immunoreactive species in control and inflamed extracts to be dynorphin A 1-8. In situ hybridization in spinal cord after administration of the inflammatory agent, carrageenan, showed increased expression of prodynorphin (Pdyn) mRNA somatotopically in medial superficial dorsal horn neurons. The fold increase in preproenkephalin mRNA (Penk) was comparatively lower, although the basal expression is substantially higher than Pdyn. While Pdyn is not expressed in the dorsal root ganglion (DRG) in basal conditions, it can be induced by nerve injury, but not by inflammation alone. A bioinformatic meta-analysis of multiple nerve injury datasets confirmed Pdyn upregulation in DRG across different nerve injury models. These data support the idea that activation of endogenous opioids, notably dynorphin, is a dynamic indicator of persistent pain states in spinal cord and of nerve injury in DRG. PERSPECTIVE: This is a systematic, quantitative assessment of dynorphin and enkephalin peptides and mRNA in dorsal spinal cord and DRG neurons in response to peripheral inflammation and axotomy. These studies form the foundational framework for understanding how endogenous spinal opioid peptides are involved in nociceptive circuit modulation.
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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.
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