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Root Ganglion (root + ganglion)
Kinds of Root Ganglion Terms modified by Root Ganglion Selected AbstractsNERVE GROWTH FACTOR RESCUE OF CISPLATIN NEUROTOXICITY IS MEDIATED THROUGH THE HIGH AFFINITY RECEPTOR: STUDIES IN PC12 CELLS AND P75 NULL MOUSE DORSAL ROOT GANGLIAJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002SJ Fischer Nerve growth factor (NGF) rescues dorsal root ganglion neurons and PC12 cells from cisplatin-induced cell death. Two model systems were used to demonstrate that rescue is mediated through the high affinity NGF receptor. In dorsal root ganglion (DRG) neurons isolated from p75(,/,) and control mice, 20 ng/ml NGF completely prevented cisplatin-induced death. In PC12 cells, we overexpressed receptor chimeras between the tumor necrosis factor and NGF receptors. We demonstrated that activation of the intracellular domain of Trk A is responsible for the NGF rescue effect. [source] FORMALIN-INDUCED INCREASE IN P2X3 RECEPTOR EXPRESSION IN DORSAL ROOT GANGLIA: IMPLICATIONS FOR NOCICEPTIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2009Ai-Hua Pan SUMMARY 1ATP-gated P2X receptors in nociceptive sensory neurons participate in the transmission of pain signals from the periphery to the spinal cord. The effect of formalin on the expression of P2X3 receptors in dorsal root ganglia (DRG) was characterized using molecular and immunological approaches and the patch-clamp technique. 2Adult Sprague-Dawley rats were injected with 100 µL of 5% formalin in the planar surface of the hindpaw and were killed 30 min and 1, 3, 6, 12, 24 and 48 h later for in vitro analyses. The expression and distribution of P2X3 receptors in the lumbar spinal cord and in L5/L6 DRG were examined; 24 and 48 h after formalin injection, currents in neurons were examined using whole-cell patch-clamp recording. 3Western blots showed that anti-P2X3 antibody recognized a major monomer of approximately 64 kDa in DRG. Immunoreactivity for P2X3 receptors was detected predominantly in the cytoplasm and plasma membrane of small (< 25 µm) and middle-sized (25,50 µm) DRG neurons. Expression of the P2X3 transcript in the DRG was unchanged 30 min and 1 h after formalin injection, but increased after 12 h. There was no distinct change in P2X3 immunostaining of the spinal cord lamina at 30 min or 1 h after injection, but after 24 h P2X3 labelling increased. At 24 h after the formalin injection, currents in isolated small and middle-sized DRG neurons were increased by 1 µmol/L ,,,-methylene-ATP. These currents were completely inhibited by 1 µmol/L A-317491, a potent and selective P2X3 receptor antagonist. 4These data suggest that formalin injection leads to early upregulation of P2X3 expression in the spinal cord and DRG and that this may be one of the mechanisms giving rise to nociception. [source] The formation of the superior and jugular ganglia: Insights into the generation of sensory neurons by the neural crestDEVELOPMENTAL DYNAMICS, Issue 2 2010Hannah Thompson Abstract The superior and jugular ganglia (S/JG) are the proximal ganglia of the IXth and Xth cranial nerves and the sensory neurons of these ganglia are neural crest derived. However, it has been unclear the extent to which their differentiation resembles that of the Dorsal Root Ganglia (DRGs). In the DRGs, neural crest cells undergo neuronal differentiation just after the onset of migration and there is evidence suggesting that these cells are pre-specified towards a sensory fate. We have analysed sensory neuronal differentiation in the S/JG. We show, in keeping with previous studies, that neuronal differentiation initiates long after the cessation of neural crest migration. We also find no evidence for the existence of migratory neural crest cells pre-specified towards a sensory phenotype prior to ganglion formation. Rather our results suggest that sensory neuronal differentiation in the S/JG is the result of localised spatiotemporal cues. Developmental Dynamics 239:439,445, 2010. © 2009 Wiley-Liss, Inc. [source] Trans-facet Joint Approach to Pulsed Radiofrequency Ablation of the L5 Dorsal Root Ganglion in a Patient with Degenerative Spondylosis and ScoliosisPAIN PRACTICE, Issue 3 2008David Abejón MD, FIPP ,,Abstract: Mechanical low back pain secondary to degenerative facet joint changes is a common reason for referral to pain clinics. When these changes cause encroachment into the intervertebral foramen, radicular pain may result. While pulsed radiofrequency of the dorsal root ganglion can be used in this setting, the anatomic deformity may make the transforaminal approach difficult. We report a case where a trans-facet approach was used successfully and describe the technique.,, [source] Localization of Vesicular Glutamate Transporter 2 mRNA in the Dorsal Root Ganglion of the Pigeon (Columba Livia)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2009Y. Atoji Summary Our previous study showed localization of glutamate receptor 1 (GluR1) mRNA in neurons of the pigeon spinal cord, suggesting glutamatergic input from intrinsic and extrinsic origins. The present study examined localization of vesicular glutamate transporter 2 (VGLUT2) mRNA to confirm an extrinsic origin of glutamatergic neurons in the dorsal root ganglion (DRG). GluR1 and GluR2 mRNAs were examined in DRG and spinal cord to seek projection regions from VGLUT2 mRNA-expressing neurons. VGLUT2 mRNA was expressed in most DRG neurons and labelling intensity varied from weakly to intensely. Intense VGLUT2 mRNA expression was mainly seen in medium to large neurons. GluR1 and GluR2 mRNAs were expressed in the dorsal horn and GluR2 mRNA signal was also seen in the marginal nucleus. The results suggest that the pigeon DRG has an extrinsic glutamatergic origin that project to the dorsal horn and marginal nucleus of the spinal cord. [source] Segmental expression of the T-box transcription factor, Tbx2, during early somitogenesisDEVELOPMENTAL DYNAMICS, Issue 11 2006Zachary Harrelson Abstract Tbx2 belongs to the T-box transcription factor gene family and is expressed in a variety of tissues and structures throughout development, although not all expression domains have been thoroughly described. Two areas of segmented expression along the rostral-caudal axis of E10.5,11.5 embryos were identified as inter-somitic vessels and dorsal root ganglia. In addition, Tbx2 expression is observed during somitogenesis beginning at E9.5, both in the posterior half of prospective somites and in a progressively restricted pattern in recently formed somites. Developmental Dynamics 235:3080,3084, 2006. © 2006 Wiley-Liss, Inc. [source] cadherin-6 Message expression in the nervous system of developing zebrafishDEVELOPMENTAL DYNAMICS, Issue 1 2006Qin Liu Abstract Cadherins are cell surface adhesion molecules that play important roles in development of a variety of tissues including the nervous system. In this study, we analyzed expression pattern of cadherin-6, a member of the type II cadherin subfamily, in the embryonic zebrafish nervous system using in situ hybridization methods. cadherin-6 message is first expressed by the neural keel, then by restricted regions in the brain and spinal cord. cadherin-6 expression in the brain transiently delineates specific brain regions. In the peripheral nervous system, cadherin-6 message is expressed by the neurogenic placodes and the dorsal root ganglia. As development proceeds, cadherin-6 expression domain and/or expression levels increased in the embryonic nervous system. Our results show that cadherin-6 expression in the zebrafish developing nervous system is both spatially and temporally regulated, implicating a role for cadherin-6 in the formation of these nervous structures. Developmental Dynamics 235:272,278, 2006. © 2005 Wiley-Liss, Inc. [source] Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous systemDEVELOPMENTAL DYNAMICS, Issue 3 2005Carles Gaston-Massuet Abstract Zic genes comprise a family of transcription factors, characterized by the presence of a zinc-finger domain containing two cysteines and two histidines (C2-H2). Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention. We studied the expression of Zic4 by in situ hybridization during mouse embryogenesis. Zic4 mRNA was first detected at low intensity at embryonic day (E) 9 and, by E10.5, expression was up-regulated in the dorsal midline of the forebrain with a strong, expanded expression domain at the boundary between the diencephalon and telencephalon, the septum, and the lamina terminalis. The choroid plexus of the third ventricle expresses Zic4, as does the dorsal part of the spinal neural tube, excluding the roof plate. The dorsal sclerotome and the dorsomedial lip of the dermomyotome also express Zic4 whereas dorsal root ganglia are negative. At E12.5, Zic4 continues to be expressed in the midline of the forebrain and in the dorsal spinal neural tube. Postnatally, Zic4 is expressed in the granule cells of the postnatal day 2 cerebellum, and in the periventricular thalamus and anterior end of the superior colliculus. We conclude that Zic4 has an expression pattern distinct from, but partly overlapping with, other members of the Zic gene family. Developmental Dynamics 233:1110,1115, 2005. © 2005 Wiley-Liss, Inc. [source] Developmental changes in neurite outgrowth responses of dorsal root and sympathetic ganglia to GDNF, neurturin, and arteminDEVELOPMENTAL DYNAMICS, Issue 3 2003H. Yan Abstract The ability of glial cell line,derived neurotrophic factor (GDNF), neurturin, and artemin to induce neurite outgrowth from dorsal root, superior cervical, and lumbar sympathetic ganglia from mice at a variety of development stages between embryonic day (E) 11.5 and postnatal day (P) 7 was examined by explanting ganglia onto collagen gels and growing them in the presence of agarose beads impregnated with the different GDNF family ligands. Artemin, GDNF, and neurturin were all capable of influencing neurite outgrowth from dorsal root and sympathetic ganglia, but the responses of each neuron type to the different ligands varied during development. Neurites from dorsal root ganglia responded to artemin at P0 and P7, to GDNF at E15.5 and P0, and to neurturin at E15.5, P0, and P6/7; thus, artemin, GDNF, and neurturin are all capable of influencing neurite outgrowth from dorsal root ganglion neurons. Neurites from superior cervical sympathetic ganglia responded significantly to artemin at E15.5, to GDNF at E15.5 and P0, and to neurturin at E15.5. Neurites from lumbar sympathetic ganglia responded to artemin at all stages from E11.5 to P7, to GDNF at P0 and P7 and to neurturin at E11.5 to P6/7. Combined with the data from previous studies that have examined the expression of GDNF family members, our data suggest that artemin plays a role in inducing neurite outgrowth from young sympathetic neurons in the early stages of sympathetic axon pathfinding, whereas GDNF and neurturin are likely to be important at later stages of sympathetic neuron development in inducing axons to enter particular target tissues once they are in the vicinity or to induce branching within target tissues. Superior cervical and lumbar sympathetic ganglia showed temporal differences in their responsiveness to artemin, GDNF, and neurturin, which probably partly reflects the rostrocaudal development of sympathetic ganglia and the tissues they innervate. Developmental Dynamics 227:395,401, 2003. © 2003 Wiley-Liss, Inc. [source] MafA transcription factor identifies the early ret-expressing sensory neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2010Laure Lecoin Abstract Dorsal root ganglia proceed from the coalescence of cell bodies of sensory neurons, which have migrated dorsoventrally from the delaminating neural crest. They are composed of different neuronal subtypes with specific sensory functions, including nociception, thermal sensation, proprioception, and mechanosensation. In contrast to proprioceptors and thermonociceptors, little is known about the molecular mechanisms governing the early commitment and later differentiation into mechanosensitive neurons. This is mainly due to the absence of specific molecular markers for this particular cell type. Using knockout mice, we identified the bZIP transcription factor MafA as the first specific marker of a subpopulation of "early c-ret" positive neurons characterized by medium-to-large diameters. This marker will allow further functional characterization of these neurons. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:485,497, 2010 [source] GPR30 estrogen receptor agonists induce mechanical hyperalgesia in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2008Julia Kuhn Abstract We evaluated the signalling pathway by which estrogen acts in peripheral tissue to produce protein kinase C, (PKC,)-dependent mechanical hyperalgesia. Specific agonists for the classical estrogen receptors (ER), ER, and ER,, did not result in activation of PKC, in neurons of dissociated rat dorsal root ganglia. In contrast, G-1, a specific agonist of the recently identified G-protein-coupled estrogen receptor, GPR30, induced PKC, translocation. Involvement of GPR30 and independence of ER, and ER, was confirmed using the GPR30 agonist and simultaneous ER, and ER, antagonist ICI 182,780 (fulvestrant). The GPR30 transcript could be amplified from dorsal root ganglia tissue. We found estrogen-induced as well as GPR30-agonist-induced PKC, translocation to be restricted to the subgroup of nociceptive neurons positive for isolectin IB4 from Bandeiraea simplicifolia. Corroborating the cellular results, both GPR30 agonists, G-1 as well as ICI 182,780, resulted in the onset of PKC,-dependent mechanical hyperalgesia if injected into paws of adult rats. We therefore suggest that estrogen acts acutely at GPR30 in nociceptors to produce mechanical hyperalgesia. [source] Peripheral antinociceptive effect of pertussis toxin: activation of the arginine/NO/cGMP/PKG/ ATP-sensitive K+ channel pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Gerly A. C. Brito Abstract The aim of the present study was to determine the effect of pertussis toxin (PTX) on inflammatory hypernociception measured by the rat paw pressure test and to elucidate the mechanism involved in this effect. In this test, prostaglandin E2 (PGE2) administered subcutaneously induces hypernociception via a mechanism associated with neuronal cAMP increase. Local intraplantar pre-treatment (30 min before), and post-treatment (5 min after) with PTX (600 ng/paw1, in 100 µL) reduced hypernociception induced by prostaglandin E2 (100 ng/paw, in 100 µL, intraplantar). Furthermore, local intraplantar pre-treatment (30 min before) with PTX (600 ng/paw, in 100 µL) reduced hypernociception induced by DbcAMP, a stable analogue of cAMP (100 µg/paw, in 100 µL, intraplantar), which indicates that PTX may have an effect other than just Gi/G0 inhibition. PTX-induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L-NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP-sensitive K+ channel (Kir6) blockers (glybenclamide and tolbutamide). In addition, PTX was shown to induce nitric oxide (NO) production in cultured neurons of the dorsal root ganglia. In conclusion, this study shows a peripheral antinociceptive effect of pertussis toxin, resulting from the activation of the arginine/NO/cGMP/PKG/ATP-sensitive K+ channel pathway. [source] Inflammation alters somatostatin mRNA expression in sensory neurons in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Seham A. Abd El-Aleem Abstract Proinflammatory neuropeptides, such as substance P and calcitonin gene-related peptide, are up-regulated in primary afferent neurons in acute and chronic inflammation. While these neuropeptides have been intensively studied, potentially anti-inflammatory and/or anti-nociceptive neuropeptides such as somatostatin (SS) have been less widely investigated. Endogenous somatostatin is thought to exert a tonic antinociceptive effect. Exogenous SS is anti-inflammatory and antinociceptive and is thought to exert these actions through inhibition of proinflammatory neuropeptide release. In this study we have compared the expression of somatostatin in two inflammatory models: arthritis, a condition associated with increased nociception, and periodontitis, in which there is little evidence of altered nociceptive thresholds. In acute arthritis (< 24 h) SS mRNA was down-regulated in ipsilateral dorsal root ganglia (DRG; 52 ± 7% of control, P < 0.05), and up-regulated in contralateral DRG (134 ± 10% of control; P < 0.05). In chronic arthritis (14 days) this pattern of mRNA regulation was reversed, with SS being up-regulated ipsilaterally and down-regulated contralaterally. In chronic mandibular periodontitis (7,10 days), SS mRNA was up-regulated in only the mandibular division of the ipsilateral trigeminal ganglion (TG) (day 7, 219 ± 9% and day 10, 217 ± 12% of control; P < 0.02) but showed no change in other divisions of the trigeminal ganglion or in the mesencephalic nucleus. These data show that antinociceptive and anti-inflammatory neuropeptides are also regulated in inflammation. It is possible that the degree of inflammation and nociception seen may depend on the balance of pro- and anti-inflammatory and nociceptive peptide expression in a particular condition. [source] c-Src kinase activation regulates preprotachykinin gene expression and substance P secretion in rat sensory gangliaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Orisa J. Igwe Abstract Increased synthesis of substance P (SP) in the dorsal root ganglia (DRG) and enhanced axonal transport to and secretion from the primary afferent sensory neurons might enhance pain signalling in the spinal dorsal horn by modifying pronociceptive pathways. IL-1, increases SP synthesis by enhancing the expression of preprotachykinin (PPT) mRNA encoding for SP and other tachykinins in the DRG. Stimulation of IL-1 receptor by IL-1, may induce the phosphorylation of tyrosine residues in many effector proteins through the activation of p60c-src kinase. The hypothesis that the synthesis of SP in and secretion from the primary sensory ganglia are regulated by the activation of p60c-src kinase induced by IL-1, was tested. Pretreatment of DRG neurons in culture with herbimycin A, genistein or PP2, three structurally different nonreceptor tyrosine kinase inhibitors that act by different mechanisms, decreased the kinase activity of p60c-src induced by the activation of IL-1 receptor. PP3, a negative control for the Src family of tyrosine kinase inhibitor PP2 had no effect. Herbimycin A and genistein also decreased IL-1,-induced expression of PPT mRNA-encoding transcripts and the levels of SP-li synthesized in the cells and secreted into the culture medium in a concentration-dependent manner. SB 203580 [a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor] and PD 98059 (a p44/42 MAPK kinase inhibitor) were ineffective in modulating IL-1,-induced SP synthesis and secretion, and p60c-src kinase activity in DRG neurons. Whereas, IL-1 receptor antagonist and cycloheximide inhibited IL-1,-evoked secretion of SP-like immunoreactivity (SP-li), actinomycin D decreased it significantly but did not entirely abolish it. These findings show that phosphorylation of specific protein tyrosine residue(s) following IL-1 receptor activation might play a key role in IL-1, signalling to modulate PPT gene expression and SP secretion in sensory neurons. In view of the role of SP as an immunomodulator, these studies provide a new insight into neural-immune intercommunication in pain regulation in the sensory ganglia through the IL-1,-induced p60c-src activation. [source] Neuronal nitric oxide synthase (nNOS) mRNA is down-regulated, and constitutive NOS enzymatic activity decreased, in thoracic dorsal root ganglia and spinal cord of the rat by a substance P N-terminal metaboliteEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Katalin J. Kovacs Abstract Nitric oxide (NO) in the spinal cord plays a role in sensory and autonomic activity. Pain induced by acetic acid in the abdominal stretch (writhing) assay and hyperalgesia associated with chronic pain are highly sensitive to NO synthase (NOS) inhibitors. Because substance P (SP) is released and up-regulated in some models of chronic pain, we hypothesized that an accumulation of SP metabolites may influence NOS expression and activity. To test this hypothesis, we examined the effect of intrathecally (i.t.) injected substance P (1-7) [SP(1-7)], the major metabolite of SP in the rat, on neuronal NOS (nNOS) mRNA in the thoracic and lumbar spinal cord, dorsal root ganglia (DRG) and on the corresponding constitutive NOS (cNOS) enzyme activity. Detected using quantitative RT-PCR, nNOS mRNA content in the thoracic spinal cord was decreased 6 h after injection of 5 µmol of SP(1-7) and returned to control 2 days later. In thoracic DRG, nNOS mRNA was reduced 48 h after SP(1-7). The cNOS enzymatic activity in thoracic spinal tissue was gradually decreased to a minimum at 72 h. Down-regulation of NOS by SP(1-7) in the thoracic area appears to be highly associated with capsaicin-sensitive primary afferent neurons. No similar changes in either parameter were measured in the lumbar area after SP(1-7). These data suggest that N-terminal SP fragments, which are known to cause long-term antinociception in the writhing assay, may do so by their ability to down-regulate NO synthesis along nociceptive pathways. [source] Induction of neuropeptides in skin innervating sensory neurons by stress and nerve growth factor as a possible reason for hair growth alterationEXPERIMENTAL DERMATOLOGY, Issue 9 2004A. Kuhlmei Recently, we introduced a mouse model launching experimental evidence for stress-induced hair growth inhibition (HGI), pointing to the existence of a brain-hair follicle axis (BFA). We suggested that nerve growth factor (NGF), besides neuropeptide substance P (SP), is a candidate mediator along the BFA. Published data further indicate that stress-related neuropeptides, e.g. calcitonin gene-related peptide (CGRP) and SP may be involved in HGI. SP and CGRP are synthesized in dorsal root ganglia (DRG) and released after axonal transport in the skin. Thus, aim of the present study was to investigate the effect of stress or subcutaneous injection of NGF, which mimics stress and regulates neuropeptide genes in sensory neurons, on the expression of SP and CGRP in DRG. Anagen was induced in C57BL/6 mice by depilation and retrograde tracing was employed on day 9 post-depilation (PD). On day 14 PD, mice were either exposed to sound stress (n = 4) injected subcutaneously with NGF (n = 4) or served as control (n = 4). On day 16 PD, DRG (mean of 30/mouse) were harvested and SP and CGRP in skin-specific sensory neurons, as identified by the tracer dye, were labelled by immunohistochemistry and counted. Stress exposure as well as NGF injection leads to a significant induction of SP and CGRP in retrograde-labelled neurons. This allows us to conclude that sensitive dermal nerve fibres are likely to originate from the presently identified neuropeptide-positive neurons. Peripheral activation of SP-expressing afferent nerve fibres via NGF-dependent pathways may cause neurogenic inflammation, eventually resulting in HGI. [source] Fabrication of Density Gradients of Biodegradable Polymer Microparticles and Their Use in Guiding Neurite OutgrowthADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Xiaoran Li Abstract A new method for generating both continuous and discrete density gradients in microparticles of biodegradable polymers via an electrospray technique is reported. The gradients are generated by spatially varying the deposition time of electrosprayed microparticles. The substrate coated with a density gradient of microparticles has varying surface roughness, offering a unique system for studying the effect of physical cues on neurite outgrowth from dorsal root ganglia. An optimal surface roughness for promoting neuron adhesion and neurite extension in vitro is obtained. Furthermore, this capability of approach is extended to generate a gradient of fluorescein isothiocyanate labeled bovine serum albumin by encapsulating it in the polymer microparticles in situ during electrospray. Taken together, this new class of substrates with gradients of microparticle density can potentially be used in various biomedical applications such as neural tissue engineering. [source] Tamoxifen modulates apoptosis in multiple modes of action in CreER miceGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 12 2008Hirohide Takebayashi Abstract Tamoxifen-inducible Cre (CreER) has become a powerful tool for in vivo manipulation of the genome. Here, we investigated opposing effects of tamoxifen on apoptosis during embryogenesis using Olig2,CreER knock-in mice, namely, tamoxifen-induced apoptosis through CreER-mediated toxicity and cytoprotective activity of tamoxifen independent of CreER. First, we examined tamoxifen-induced apoptosis; in the homozygous mice, we observed region-specific apoptosis in the ventral neural tube, with no obvious increase in the heterozygotes. Next, we detected a cytoprotective effect on apoptosis in the homozygous dorsal root ganglia (DRG). This apoptosis is a secondary phenotype of Olig2 -null mice, as Olig2/CreER is not expressed in the DRG. The cytoprotective effect is DRG-specific, because tamoxifen did not rescue apoptosis in the interdigital mesenchyme. These data indicate that tamoxifen has multiple effects on apoptosis during development and caution that careful examination is necessary when interpreting results obtained from tamoxifen-induced recombination: in Olig2-CreER mice, heterozygotes are usable for lineage-tracing experiment without obvious toxicity, while homozygotes show efficient recombination, despite enhanced apoptosis. genesis 46:775,781, 2008. © 2008 Wiley-Liss, Inc. [source] Generation of a transgenic mouse line expressing GFP-Cre protein from a Hoxb4 neural enhancerGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2008Elena Rivkin Abstract Here, we describe a transgenic mouse line, in which expression of green fluorescent protein fused to Cre recombinase (GFP-Cre) is directed by the early neuronal enhancer (ENE) of Hoxb4. In E9.0,13.5 transgenic embryos, Cre activity coincided with endogenous Hoxb4 throughout the neural tube up to the r6/r7 boundary in the hindbrain, the dorsal root ganglia, and the Xth cranial ganglia. Unexpectedly, Cre activity was also consistently detected in the trigeminal (Vth) cranial nerve, which is devoid of endogenous Hoxb4 expression. Strong GFP dependent fluorescence appeared slightly later in E9.5,E11.5 embryos, and reflected the later expression pattern expected for Hoxb4-ENE directed expression in the neural tube up to the r7/r8 not r6/r7 boundary. Thus, with the exception of the trigeminal nerve, this reporter faithfully reproduces endogenous embryonic neural Hoxb4 expression, and provides an excellent reagent for in vivo gene manipulations in neuronal Hoxb4 positive cells as well as the developing trigeminal nerve. This transgenic mouse line should prove especially useful for determining the fate map of neuronal populations arising in rhombomeres 7 and 8 on its own and in combination with the small set of other existing rhombomere-specific Cre recombinase expressing lines. genesis 46:119,124, 2008. © 2008 Wiley-Liss, Inc. [source] Conductive Core,Sheath Nanofibers and Their Potential Application in Neural Tissue EngineeringADVANCED FUNCTIONAL MATERIALS, Issue 14 2009Jingwei Xie Abstract Conductive core,sheath nanofibers are prepared by a combination of electrospinning and aqueous polymerization. Specifically, nanofibers electrospun from poly(, -caprolactone) (PCL) and poly(L -lactide) (PLA) are employed as templates to generate uniform sheaths of polypyrrole (PPy) by in-situ polymerization. These conductive core,sheath nanofibers offer a unique system to study the synergistic effect of different cues on neurite outgrowth in vitro. It is found that explanted dorsal root ganglia (DRG) adhere well to the conductive core,sheath nanofibers and generate neurites across the surface when there is a nerve growth factor in the medium. Furthermore, the neurites can be oriented along one direction and enhanced by 82% in terms of maximum length when uniaxially aligned conductive core,sheath nanofibers are compared with their random counterparts. Electrical stimulation, when applied through the mats of conductive core,sheath nanofibers, is found to further increase the maximum length of neurites for random and aligned samples by 83% and 47%, respectively, relative to the controls without electrical stimulation. Together these results suggest the potential use of the conductive core,sheath nanofibers as scaffolds in applications such as neural tissue engineering. [source] Chronic constriction injury induces aquaporin-2 expression in the dorsal root ganglia of ratsJOURNAL OF ANATOMY, Issue 5 2009Barbara Buffoli Abstract Aquaporins are a family of water channel proteins involved in water homeostasis in several tissues. Current knowledge of aquaporin expression in the nervous system is very limited. Therefore the first aim of this study was to assess, by immunohistochemistry and immunoblotting analysis, the presence and localization of aquaporin-2 in the spinal cord and dorsal root ganglia of naïve adult rats. In addition, we evaluated aquaporin-2 expression in response to chronic constriction injury of the sciatic nerve, a model of neuropathic pain. Our results showed that aquaporin-2 expression was not detectable either in the spinal cord or the dorsal root ganglia of naïve rats. However, we showed for the first time an increase of aquaporin-2 expression in response to chronic constriction injury treatment in small-diameter dorsal root ganglia neurons but no expression in the lumbar spinal cord. These data support the hypothesis that aquaporin-2 expression is involved in inflammatory neuropathic nerve injuries, although its precise role remains to be determined. [source] Varicella-zoster virus isolates, but not the vaccine strain OKA, induce sensitivity to alpha-1 and beta-1 adrenergic stimulation of sensory neurones in cultureJOURNAL OF MEDICAL VIROLOGY, Issue S1 2003Michaela Schmidt Abstract The reactivation of varicella-zoster virus (VZV) from its persistent state in sensory neurones causes shingles and induces severe, long-lasting pain and hyperalgesia that often lead to postherpetic neuralgia. To investigate the VZV-induced neuropathic changes, we established conditions for the active infection of sensory neurones from rat dorsal root ganglia in vitro. After 2 days of culture, up to 50% of the cells expressed viral antigens of the immediate-early and late replication phase. The intracellular calcium ion concentration was monitored in individual cells by microfluorimetry. Whereas the calcium response to capsaicin was preserved, the VZV-infected neurones gained an unusual sensitivity to noradrenaline stimulation in contrast to non-infected cells. The adrenergic agonists phenylephrine and isoproterenol had a similar efficacy demonstrating that both ,1 - and ,1 -adrenoreceptors were involved. The sensitivity to adrenergic stimulation was observed after infection with different wildtype isolates, but not with the attenuated vaccine strain OKA. The lack of noradrenaline sensitivity of vaccine-infected neurones demands a structural comparison of wildtype and vaccine viruses with and without phenotype. A partial sequence evaluation (26 kb) of the European OKA vaccine strain surprisingly revealed a series of nucleotide exchanges in comparison to presumably identical OKA strains from other sources, although VZV is generally considered genetically stable. In summary, we report that the infection with wildtype VZV isolates, but not with the vaccine strain, induces noradrenaline sensitivity in sensory neurones, which correlates with clinical and experimental observations of adrenergic effects involved in VZV-induced neuralgia. J. Med. Virol. 70:S82,S89, 2003. © 2003 Wiley-Liss, Inc. [source] Nociceptive and behavioural sensitisation by protein kinase C, signalling in the CNSJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Kristof Van Kolen Abstract Despite the apparent homology in the protein kinase C (PKC) family, it has become clear that slight structural differences are sufficient to have unique signalling properties for each individual isoform. For PKC, in depth investigation of these aspects revealed unique actions in the CNS and lead to development of specific modulators with clinical perspective. In this review, we describe to which extent PKC, is distinct from other isoforms on the level of tissue expression and protein structure. As this kinase is highly expressed in the brain, we outline three main aspects of PKC, signalling in the CNS. First, its ability to alter the permeability of N-type Ca2+ channels in dorsal root ganglia has been shown to enhance nociception. Secondly, PKC, increases anxiety by diminishing GABAAR-induced inhibitory post-synaptic currents in the prefrontal cortex. Another important aspect of the latter inhibition is the reduced sensitivity of GABAA receptors to ethanol, a mechanism potentially contributing to abuse. A third signalling cascade improves cognitive functions by facilitating cholinergic signalling in the hippocampus. Collectively, these findings point to a physical and behavioural sensitising role for this kinase. [source] Defective axonal transport of neurofilament proteins in neurons overexpressing peripherinJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Stéphanie Millecamps Abstract Peripherin is a type III neuronal intermediate filament detected in motor neuron inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously reported that overexpression of peripherin provokes late-onset motor neuron dysfunction in transgenic mice. Here, we show that peripherin overexpression slows down axonal transport of neurofilament (NF) proteins, and that the transport defect precedes by several months the appearance of axonal spheroids in adult mice. Defective NF transport by peripherin up-regulation was further confirmed with dorsal root ganglia (DRG) neurons cultured from peripherin transgenic embryos. Immunofluorescence microscopy and western blotting revealed that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H species in DRG neurites. Similarly the transport of a green fluorescent protein (GFP)-tagged NF-M, delivered by means of a lentiviral construct, was impaired in DRG neurites overexpressing peripherin. These results demonstrate that peripherin overexpression can cause defective transport of type IV NF proteins, a phenomenon that may account for the progressive formation of ALS-like spheroids in axons. [source] Efficient gene transfer from innervated muscle into rat peripheral and central nervous systems using a non-viral haemagglutinating virus of Japan (HVJ)-liposome methodJOURNAL OF NEUROCHEMISTRY, Issue 3 2003Naoki Kato Abstract We evaluated the feasibility of gene delivery into the peripheral and central nervous systems via retrograde axonal transport following injection of a haemagglutinating virus of Japan (HVJ)-liposome-DNA complex vector into an innervated muscle. Transfection efficiency was assessed by measuring luciferase activity, and was compared statistically with that achieved using a liposome-DNA control vector. High luciferase activity was observed in the injected muscle, the ipsilateral sciatic nerve, and the ipsilateral dorsal root ganglia on day 1 after gene transfer. The spinal cord also showed luciferase activity, although this was lower than in the other tissues. However, no activity was observed in the contralateral sciatic nerve or the contralateral dorsal root ganglia. In addition, we performed gene transfer twice, with a 1-week interval, to evaluate the feasibility of repeated therapeutic gene delivery. Again, a high transfection efficiency was observed immediately, even after the second gene transfer, and transfection efficiency was significantly higher at each defined time-point using the HVJ-liposome complex vector than using a control vector. These results indicate that this method could be used for repeated therapeutic gene delivery into muscle, nerve, dorsal root ganglia, and possibly spinal cord, without the need for a surgical approach, making it well suited to clinical applications. [source] Immediate anti-tumor necrosis factor-, (etanercept) therapy enhances axonal regeneration after sciatic nerve crushJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2010Kinshi Kato Abstract Peripheral nerve regeneration begins immediately after injury. Understanding the mechanisms by which early modulators of axonal degeneration regulate neurite outgrowth may affect the development of new strategies to promote nerve repair. Tumor necrosis factor-, (TNF-,) plays a crucial role in the initiation of degenerative cascades after peripheral nerve injury. Here we demonstrate using real-time Taqman quantitative RT-PCR that, during the time course (days 1,60) of sciatic nerve crush, TNF-, mRNA expression is induced at 1 day and returned to baseline at 5 days after injury in nerve and the corresponding dorsal root ganglia (DRG). Immediate therapy with the TNF-, antagonist etanercept (fusion protein of TNFRII and human IgG), administered systemically (i.p.) and locally (epineurially) after nerve crush injury, enhanced the rate of axonal regeneration, as determined by nerve pinch test and increased number of characteristic clusters of regenerating nerve fibers distal to nerve crush segments. These fibers were immunoreactive for growth associated protein-43 (GAP-43) and etanercept, detected by anti-human IgG immunofluorescence. Increased GAP-43 expression was found in the injured nerve and in the corresponding DRG and ventral spinal cord after systemic etanercept compared with vehicle treatments. This study established that immediate therapy with TNF-, antagonist supports axonal regeneration after peripheral nerve injury. © 2009 Wiley-Liss, Inc. [source] Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion-affected expression, and impaired regenerative axonal growthJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009Bettina A. Buhren Abstract Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice. © 2009 Wiley-Liss, Inc. [source] Rapid method for culturing embryonic neuron,glial cell coculturesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003Åsa Fex Svenningsen Abstract A streamlined, simple technique for primary cell culture from E17 rat tissue is presented. In an attempt to standardize culturing methods for all neuronal cell types in the embryo, we evaluated a commercial medium without serum and used similar times for trypsinization and tested different surfaces for plating. In 1 day, using one method and a single medium, it is possible to produce robust E17 cultures of dorsal root ganglia (DRG), cerebellum, and enteric plexi. Allowing the endogenous glial cells to repopulate the cultures saves time compared with existing techniques, in which glial cells are added to cultures first treated with antimitotic agents. It also ensures that all the cells present in vivo will be present in the culture. Myelination commences after approximately 2 weeks in culture for dissociated DRG and 3,4 weeks in cerebellar cultures. In enteric cultures, glial wrapping of the enteric neurons is seen after 3 weeks (2 weeks in ascorbic acid), suggesting that basal lamina production is important even for glial ensheathment in the enteric nervous system. No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous system and central nervous system cultures was very robust. © 2003 Wiley-Liss, Inc. [source] Hyperlipidemia: a new therapeutic target for diabetic neuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2009Andrea M. Vincent Abstract Emerging data establish dyslipidemia as a significant contributor to the development of diabetic neuropathy. In this review, we discuss how separate metabolic imbalances, including hyperglycemia and hyperlipidemia, converge on mechanisms leading to oxidative stress in dorsal root ganglia (DRG) sensory neurons. We conclude with suggestions for novel therapeutic strategies to prevent or reverse diabetes-induced nerve degeneration. [source] Activation Of Mitogen Activated Protein Kinases (Mapks) In Response To High Glucose In Primary Sensory NeuronesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000T Purves In diabetes high glucose stresses cells as a prelude to complications. The MAPKs are serine-threonine kinases, which are putative glucose stress transducers, comprising extracellular signal regulated kinases (ERKs), p38 and c-Jun, n-terminal kinases (JNKs). In 10 week streptozotocin-induced diabetic rats JNK activation was increased when compared to age matched controls. This study aimed to determine the signaling pathways activated in response to high glucose in adult sensory neurones in vitro. Cultures of adult rat dorsal root ganglia (DRG) were treated with 10mM, 25mM and 50mM glucose for 16 hours. MAPK activation was examined in Western blots using antibodies raised against phosphorylated and non-phosphorylated epitopes (results expressed as a ratio of phosphorylated to non-phosphorylated kinase). Glucose caused a concentration-dependent increase in phospho-p38 with a 1.6 fold increase at 25mM (0.77 ± 1.04) and a 2.4 fold increase at 50mM (1.18 ± 1.44) when compared to 10mM (0.49 ± 0.60) glucose. Phosphorylation of the p56 JNK isoform increased 2.4 fold (4.37 ± 3.59) and the p46 isoform 2.2 fold (1.95 ± 1.35) at 50mM glucose when compared to 10mM (p56 1.80 ± 0.99, p46 0.88 ± 0.31). ERK phosphorylation remained unchanged in 3 different experiments. Immunocytochemistry located these changes to neurones, rather than the small percentage of non-neurones that remain in culture. Transcription factor activation as a result of MAPK activation is being investigated using electrophoretic mobility shift assays. We conclude that the activation of MAPK pathways is involved in the response of neuronal cells to high glucose stress. [source] | |||||||||||||||||||||||||||||||