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Isolectin B4 (isolectin + b4)
Selected AbstractsGDNF hyperalgesia is mediated by PLC,, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versicanEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Oliver Bogen Abstract The function of the isolectin B4 (IB4+)-binding and GDNF-dependent Ret (Ret+)-expressing non-peptidergic subpopulation of nociceptors remain poorly understood. We demonstrate that acute administration of GDNF sensitizes nociceptors and produces mechanical hyperalgesia in the rat. Intrathecal IB4,saporin, a selective toxin for IB4+/Ret+ -nociceptors, attenuates GDNF but not NGF hyperalgesia. Conversely, intrathecal antisense to Trk A attenuated NGF but not GDNF hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides targeting mRNA for versican, the molecule that renders the Ret-expressing nociceptors IB4-positive (+), also attenuated GDNF but not NGF hyperalgesia, as did ADAMTS-4, a matrix metalloprotease known to degrade versican. Finally, inhibitors for all five signaling pathways known to be activated by GDNF at GFR,1/Ret: PLC,, CDK5, PI3K, MAPK/ERK and Src family kinases, attenuated GDNF hyperalgesia. Our results demonstrate a role of the non-peptidergic nociceptors in pain produced by the neurotrophin GDNF and suggest that the IB4-binding protein versican functions in the expression of this phenotype. [source] The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal hornEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003A. J. Todd Abstract Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94,100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III,VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter. [source] Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injuryJOURNAL OF NEUROCHEMISTRY, Issue 1 2002Natalie J. Gardiner Abstract Members of the interleukin-6 (IL-6) family of cytokines have been implicated as major mediators of the response of the adult nervous system to injury. The basis for an interaction of IL-6 cytokines with adult sensory neurones has been established by analysing the levels and distribution of the two signal-transducing receptor subunits, glycoprotein 130 (gp130) and leukaemia inhibitory factor receptor (LIFR), in the dorsal root ganglion (DRG) of male adult rats before and following nerve injury. All sensory neurones express gp130-immunoreactivity (IR) in the cytoplasm and on the plasma membrane. Levels of gp130 and its intracellular distribution remained unchanged up to 14 days following sciatic nerve axotomy. LIFR-IR was largely absent from the cytoplasm and plasma membrane of sensory neurones, but confined almost exclusively to the nuclear compartment. However, following axotomy, punctate cytoplasmic LIFR-IR was detected which persisted up to 28 days following axotomy. The expression of cytoplasmic LIFR 2 days post-axotomy was proportionally greater in a subset of small diameter sensory neurones which expressed either the sensory neuropeptide CGRP or the cell surface marker isolectin B4. The coexpression of gp130 and LIFR in the same intracellular compartment following axotomy conveys potential responsiveness of injured sensory neurones to members of the IL-6 family of cytokines. [source] Distribution of P2X3 -immunoreactive fibers in hairy and glabrous skin of the ratTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2009Anna M.W. Taylor Abstract The skin is innervated by two populations of unmyelinated sensory fibers, the peptidergic and nonpeptidergic, which transmit nociceptive information to the central nervous system. The peptidergic population expresses neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) and has both cutaneous and visceral targets. The nonpeptidergic population expresses the purinergic receptor P2X3, binds the isolectin B4 (IB4), and innervates mainly the epidermis. To date, the peptidergic nociceptor population in cutaneous tissue of the rat has been well characterized, whereas the nonpeptidergic innervation pattern has lacked an adequate description. To this aim, we used light microscopic immunocytochemistry to investigate the pattern of P2X3 -immunoreactive (-IR) fiber innervation of both hairy and glabrous skin from male Sprague-Dawley rats. Our results show extensive P2X3 -IR fibers throughout the upper and lower dermis. Thick bundles of P2X3 -IR fibers were found to run in parallel with the dermal-epidermal junction and projected multiple thin collateral axons that penetrated the epidermal layer, creating a dense network of innervation throughout the entire epidermis. The distribution of P2X3 -IR fibers in the epidermis was far more extensive than the distribution of CGRP-IR fibers. P2X3 -IR fibers also innervate hair follicles but were rarely found in close proximity to glands and blood vessels. The present results suggest a primary role for P2X3 -IR fibers in the detection of noxious stimuli in cutaneous tissue and provide an anatomical basis for future studies examining a possible functionally distinct role of nonpeptidergic nociceptors in the transmission of nociceptive signals. J. Comp. Neurol. 514:555,566, 2009. © 2009 Wiley-Liss, Inc. [source] C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axonsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005Beth Brianna Murinson Abstract Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively. Injection of IB4-conjugated horseradish peroxidase into a lumbar DRG resulted in intense labeling of IB4 axons, with very low background. Visualized by confocal fluorescence, IB4-binding and CGRP-positive nerve fibers orginating from different DRG neurons came together and remained closely parallel over long distances, suggesting that these two types of axon occupy the same Remak bundle. With double-labeling immunogold electron microscopy (EM), we confirmed that IB4 and CGRP axons were distinct and were found together in single Remak bundles. Previous studies indicate that some DRG neurons express both CGRP and IB4 binding. To ensure that our immunogold results were not a consequence of coexpression, we studied large populations of unmyelinated axons by using quantitative single-label EM. Tetramethylbenzidine, a chromogen with strong intrinsic signal amplification of IB4-horseradish peroxidase, labeled as many as 52% of unmyelinated axons in the dorsal root. Concomitantly, 97% of the Remak bundles with more than one axon contained at least one IB4-labeled axon. Probabilistic modeling using binomial distribution functions rejected the hypothesis that IB4 axons segregate into IB4-specific bundles (P < 0.00001). We conclude that most Remak bundle Schwann cells simultaneously support diverse axon types with different growth factor dependences. J. Comp. Neurol. 484:392,402, 2005. © 2005 Wiley-Liss, Inc. [source] | ||||||||||