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DRG neurons

Corey Heffernan, Patrice Maurel
Lentiviral transduction is a gene delivery method that provides numerous advantages over direct transfection and traditional retroviral or adenoviral delivery methods. It facilitates for the transduction of primary cells inherently difficult to transfect, delivers constructs of interest to nondividing as well as dividing cells, and permits the long-term expression of sizable DNA inserts (e.g., <7 kb). The study of peripheral nerve myelination at the molecular level has long benefited from the Schwann cells/dorsal root ganglia (DRG) neurons myelinating co-culture system...
2018: Methods in Molecular Biology
Thanh D Do, Joseph F Ellis, Elizabeth K Neumann, Troy J Comi, Emily G Tillmaand, Ashley E Lenhart, Stanislav S Rubakhin, Jonathan Sweedler
The mammalian dorsal root ganglia (DRG) are located on the dorsal roots of the spinal nerves and contain cell bodies of primary sensory neurons. DRG cells have been classified into subpopulations based on their size, morphology, intracellular markers, response to stimuli, and neuropeptides. To understand the connections between DRG chemical heterogeneity and cellular function, we performed optically guided, high-throughput single cell profiling using sequential matrix-assisted laser desorption/ionization mass spectrometry (MS) to detect lipids, peptides, and several proteins in individual DRG cells...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nirupa D Jayaraj, Bula J Bhattacharyya, Abdelhak A Belmadani, Dongjun Ren, Craig A Rathwell, Sandra Hackelberg, Brittany E Hopkins, Herschel R Gupta, Richard J Miller, Daniela M Menichella
Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN...
March 13, 2018: Journal of Clinical Investigation
Pini Koplovitch, Marshall Devor
Ectopic impulse discharge (ectopia) generated in the soma of afferent neurons in dorsal root ganglia (DRGs) following nerve injury is thought to be a major contributor to neuropathic pain. The DRG is thus a prime interventional target. The process of electrogenesis (impulse generation) in the DRG is far more sensitive to systemically administered Na channel blockers than the process of impulse propagation along sensory axons. It should therefore be possible to selectively suppress DRG ectopia with local application of membrane stabilizing agents without blocking normal impulse traffic...
March 12, 2018: Pain
Zachary Jonas Hall, Vincent Tropepe
The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons...
March 12, 2018: ELife
Zachariah J Sperry, Kyounghwan Na, Saman S Parizi, Hillel J Chiel, John Seymour, Euisik Yoon, Tim M Bruns
The dorsal root ganglia (DRG) are promising nerve structures for sensory neural interfaces because they provide centralized access to primary afferent cell bodies and spinal reflex circuitry. In order to harness this potential, new electrode technologies are needed which take advantage of the unique properties of DRG, specifically the high density of neural cell bodies at the dorsal surface. Here we report initial &lt;i&gt;in vivo&lt;/i&gt; results from the development of a flexible non-penetrating polyimide electrode array interfacing with the surface of ganglia...
March 9, 2018: Journal of Neural Engineering
Pratibha Narayanan, Meike Hütte, Galina Kudryasheva, Francisco J Taberner, Stefan G Lechner, Florian Rehfeldt, David Gomez-Varela, Manuela Schmidt
Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2...
March 9, 2018: ELife
Gunnar Poplawski, Tetsuhiro Ishikawa, Coralie Brifault, Corinne Lee-Kubli, Robert Regestam, Kenneth W Henry, Yasuhiro Shiga, HyoJun Kwon, Seiji Ohtori, Steven L Gonias, Wendy M Campana
Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes in the transcriptome of sensory neurons, which are instrumental for axon regeneration. The role of Schwann cells (SCs) in mediating these changes remains undefined. We tested the hypothesis that SCs regulate expression of genes in sensory neurons before and after PNS injury by comparing mice in which LDL Receptor-related Protein-1 (LRP1) is deleted in SCs (scLRP1-/- mice) with wild-type (scLRP1+/+ ) littermates...
March 9, 2018: Glia
Dale George, Paige Ahrens, Stephen Lambert
Satellite glial cells (SGCs) are glial cells in the peripheral nervous system that form sheaths around the neuronal cell body. This unique arrangement of SGCs allows it to exert a highly regulated control over the neuronal microenvironment. Not much is known about the origin of SGCs. In this study, we examine the development of SGCs. We show that rat SGCs develop postnatally and these cells express a number of markers associated with Schwann cell precursors, in particular cadherin-19 (CDH19) even in adult DRGs...
March 9, 2018: Glia
Rafael Taeho Han, Han-Byul Kim, Young-Beom Kim, Kyungmin Choi, Gi Yeon Park, Pa Reum Lee, JaeHee Lee, Hye Young Kim, Chul-Kyu Park, Youngnam Kang, Seog Bae Oh, Heung Sik Na
Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH2 )5 [Tyr(Me)2 ,Dab5 ] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH2 -d(CH2 )5 [DTyr2 , Thr4 ]OVT, an oxytocin receptor antagonist...
March 2018: Korean Journal of Physiology & Pharmacology
Ricardo González-Ramírez, Elizabeth Martínez-Hernández, Alejandro Sandoval, Kimberly Gómez-Mora, Ricardo Felix
It is well known that the CaV α2 δ auxiliary subunit regulates the density of high voltage-activated Ca2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of CaV α2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of CaV α2 δ...
March 5, 2018: Neuroscience Letters
Won Jai Jung, Sang Yeub Lee, Sue In Choi, Byung-Keun Kim, Eun Joo Lee, Kwang Ho In, Min-Goo Lee
Airway sensory nerves are known to express several receptors and channels that are activated by exogenous and endogenous mediators that cause coughing. Toll-like receptor (TLR) s are expressed in nociceptive neurons and play an important role in neuroinflammation. However, there have been very few studies of TLR expression in lung-derived sensory neurons or their relevance to respiratory symptoms such as cough. We used the bleomycin-induced pulmonary fibrosis model to investigate the change in TLR expression in pulmonary neurons and the association of TLRs with transient receptor potential (TRP) channels in pulmonary neurons...
2018: PloS One
Priyanka Chauhan, Wen S Sheng, Shuxian Hu, Sujata Prasad, James R Lokensgard
BACKGROUND: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation...
March 5, 2018: Journal of Neuroinflammation
Wenying Wang, Xiaqing Ma, Limin Luo, Min Huang, Jing Dong, Xiaoli Zhang, Wei Jiang, Tao Xu
BACKGROUND AND PURPOSE: The P2X3 receptor (P2X3R) is a major receptor in the processing of nociceptive information in dorsal root ganglia (DRGs). We investigated the role of the P2X3R and the detailed mechanisms underlying chronic morphine-induced analgesic tolerance in rats. EXPERIMENTAL APPROACHES: Under isoflurane inhalation anaesthesia, intrathecal catheters were implanted in male Sprague-Dawley rats. Repeated intrathecal (i.t.) morphine treatment was used to induce anti-nociceptive tolerance...
March 3, 2018: British Journal of Pharmacology
Andrew J Shepherd, Aaron D Mickle, Suraj Kadunganattil, Hongzhen Hu, Durga P Mohapatra
Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment...
2018: Frontiers in Cellular Neuroscience
Lubin Chen, Jianying Huang, Peng Zhao, Anna-Karin Persson, Fadia B Dib-Hajj, Xiaoyang Cheng, Andrew Tan, Stephen G Waxman, Sulayman D Dib-Hajj
Voltage-gated sodium channels NaV 1.7, NaV 1.8 and NaV 1.9 have been the focus for pain studies because their mutations are associated with human pain disorders, but the role of NaV 1.6 in pain is less understood. In this study, we selectively knocked out NaV 1.6 in dorsal root ganglion (DRG) neurons, using NaV 1.8-Cre directed or adeno-associated virus (AAV)-Cre mediated approaches, and examined the specific contribution of NaV 1.6 to the tetrodotoxin-sensitive (TTX-S) current in these neurons and its role in neuropathic pain...
March 1, 2018: Scientific Reports
Petr Dubový, Ivana Hradilová-Svíženská, Ilona Klusáková, Viktoria Kokošová, Václav Brázda, Marek Joukal
Unilateral sciatic nerve compression (SNC) or complete sciatic nerve transection (CSNT), both varying degrees of nerve injury, induced activation of STAT3 bilaterally in the dorsal root ganglia (DRG) neurons of lumbar (L4-L5) as well as cervical (C6-C8) spinal cord segments. STAT3 activation was by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and was followed by their nuclear translocation. This is the first evidence of STAT3(S727) activation together with the well-known activation of STAT3(Y705) in primary sensory neurons upon peripheral nerve injury...
February 28, 2018: Histochemistry and Cell Biology
Jason A Bleedorn, Troy A Hornberger, Craig A Goodman, Zhengling Hao, Susannah J Sample, Ermias Amene, Mark D Markel, Mary Behan, Peter Muir
Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR)...
2018: PloS One
Carmen De Caro, Roberto Russo, Carmen Avagliano, Claudia Cristiano, Antonio Calignano, Andrea Aramini, Gianluca Bianchini, Marcello Allegretti, Laura Brandolini
BACKGROUND AND PURPOSE: Transient receptor potential (TRP) channels are a superfamily of non-selective cation permeable channels involved in peripheral sensory signalling. Animal studies have shown that several TRPs are relevant players in pain modulation. Among them, the TRP Melastatin8 (TRPM8) has elicited more interest for its controversial role in nociception. This channel, expressed by a subpopulation of sensory neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG), is activated by cold temperatures and cooling agents...
February 27, 2018: British Journal of Pharmacology
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