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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 20 (2004), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The peripheral benzodiazepine receptor (PBR), a benzodiazepine but not γ-aminobutyric acid-binding mitochondrial membrane protein, has roles in steroid production, energy metabolism, cell survival and growth. PBR expression in the nervous system has been reported in non-neuronal glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand, [3H]PK11195, in dorsal root ganglion (DRG) neurons following injury to the sciatic nerve. In naïve animals, PBR mRNA, protein expression and ligand binding are undetectable in the DRG. Three days after sciatic nerve transection, however, PBR mRNA begins to be expressed in injured neurons, and 4 weeks after the injury, expression and ligand binding are present in 35% of L4 DRG neurons. PBR ligand binding also appears after injury in the superficial dorsal horn of the spinal cord. The PBR expression in the DRG is restricted to small and medium-sized neurons and returns to naïve levels if the injured peripheral axons are allowed to regrow and reinnervate targets. No non-neuronal PBR expression is detected, unlike its putative endogenous ligand the diazepam binding inhibitor (DBI), which is expressed only in non-neuronal cells, including the satellite cells that surround DRG neurons. DBI expression does not change with sciatic nerve transection. PBR acting on small-calibre neurons could play a role in the adaptive survival and growth responses of these cells to injury of their axons.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 19 (2004), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Glypican-1, a glycosyl phosphatidyl inositol (GPI)-anchored heparan sulphate proteoglycan expressed in the developing and mature cells of the central nervous system, acts as a coreceptor for diverse ligands, including slit axonal guidance proteins, fibroblast growth factors and laminin. We have examined its expression in primary sensory dorsal root ganglion (DRG) neurons and spinal cord after axonal injury. In noninjured rats, glypican-1 mRNA and protein are constitutively expressed at low levels in lumbar DRGs. Sciatic nerve transection results in a two-fold increase in mRNA and protein expression. High glypican-1 expression persists until the injured axons reinnervate their peripheral targets, as in the case of a crushed nerve. Injury to the central axons of DRG neurons by either a dorsal column injury or a dorsal root transection also up-regulates glypican-1, a feature that differs from most DRG axonal injury-induced genes, whose regulation changes only after peripheral and not central axonal injury. After axonal injury, the cellular localization of glypican-1 changes from a nuclear pattern restricted to neurons in noninjured DRGs, to the cytoplasm and membrane of injured neurons, as well as neighbouring non-neuronal cells. Sciatic nerve transection also leads to an accumulation of glypican-1 in the proximal nerve segment of injured axons. Glypican-1 is coexpressed with robo 2 and its up-regulation after axonal injury may contribute to an altered sensitivity to axonal growth or guidance cues.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The N-methyl-D-aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord and the generation of pain hypersensitivity. NMDAR function is modulated by post-translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity in the spinal cord. We now show that a noxious heat stimulus applied to the rat hindpaw induces phosphorylation of the NMDAR NR1 subunit at a protein kinase C (PKC)-dependent site, serine-896, in superficial dorsal horn neurons. Phosphorylation of NR1 serine-896 is essentially absent in the superficial dorsal horn laminae of naïve rats, but there is rapid (〈 2 min) induction following a noxious but not innocuous heat stimulus. The number of pNR1-immunoreactive neuronal profiles in the superficial dorsal horn peaks 30 min after noxious heat stimulation and persists for up to 1 h. pNR1serine896 induction occurs in the endoplasmic reticulum, suggesting that it contributes to trafficking of the receptor from intracellular stores to the membrane. The phosphorylation of the subunit is attenuated by intrathecal injection of the NMDAR antagonist, MK801, suggesting that the NMDAR is involved via a feed-forward mechanism in its own phosphorylation. The pNR1serine896-positive neurons are highly co-localized with PKCdelta and only rarely with PKCgamma. These data provide evidence for an activity-dependent NMDAR phosphorylation at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons initiated by peripheral noxious stimuli.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a) was one of 240 genes found previously by high density oligonucleotide microarray analysis to be regulated in the rat L4 and L5 dorsal root ganglia 3 days after transection of the sciatic nerve (〉four-fold up-regulation). The Gadd45a mRNA expression profile investigated by northern blot, RNase protection assay and in situ hybridization in the rat shows negligible constitutive mRNA levels in embryonic, neonatal or adult intact dorsal root ganglia. Within 24 h of a sciatic nerve injury, a very large induction is found that persists for as long as regeneration of injured fibres is prevented by peripheral nerve ligation. When axons are allowed to regrow following sciatic nerve crush injury, Gadd45a expression is terminated at later time points, when levels of other markers of injury return towards normal. Colocalization with activating transcription factor 3-LI and c-jun mRNA implies that all peripherally injured primary sensory and motor neurons express Gadd45a mRNA. Injury to the central axons of dorsal root ganglion neurons produces only a minimal induction of Gadd45a while peripheral inflammation is without effect. Gadd45a is a specific marker of the presence of peripheral axonal injury in adult primary sensory and motor neurons.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that ...
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  • 6
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The cutaneous receptive fields of flexor motor neurons expand in size and increase in responsiveness after peripheral tissue injury5'6. Similar effects can be produced by brief conditioning volleys in unmyelinated afferents, with muscle afferents having a more prolonged effect than cutaneous ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 449 (2007), S. 607-610 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Most local anaesthetics used clinically are relatively hydrophobic molecules that gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane. These anaesthetics block sodium channels and thereby the excitability of all neurons, not just sensory ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Inflammation causes the induction of cyclooxygenase-2 (Cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue ...
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 413 (2001), S. 378-378 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ...Major advances in biomedicine — such as the decoding of the human genome — increasingly depend on the application of ever more complex technologies, the harnessing of large teams of scientists and technicians, and the acquisition and management of huge budgets. Some of the most ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 355 (1992), S. 75-78 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Peripheral nerve injury in humans is associated with decreased or abnormal sensations, including pain8'12. Here we examined whether structural changes in the central terminals of the axotomized primary afferent neurons have a particular role in the development of these sensory ...
    Type of Medium: Electronic Resource
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