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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have probed the molecular basis of functional effects of ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF) on aspects of the neuronal differentiation of LA-N-2 neuroblastoma cells. The influence of CNTF on the cholinergic phenotype can be accounted for by transcriptional/translational effects without implicating posttranslational mechanisms. Although both NGF receptors are expressed constitutively by LA-N-2 cells, CNTF has a marked stimulatory effect on trkA mRNA and protein. The NGF receptors are functional in serum-free conditions where they mitigate CNTF effects on cell adhesion but do not support process extension. Following priming by CNTF, NGF and CNTF have synergistic influences on process formation but not on choline acetyltransferase-specific activity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 16 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been suggested that altered retrograde neurotrophin support contributes to the phenotypic switch observed in BDNF expression in injured sensory neurons. Thus, modulatory influences of NGF and NT-3 on BDNF expression in injured adult rat DRG neurons were examined using in situ hybridization and immunohistochemical approaches. Quantitative analysis reveals a biphasic response to sciatic nerve injury, whereby in the first day following injury, BDNF expression is up-regulated in ≈83% of injured neurons including all small neurons, and a larger pool of trkB expressing neurons than in intact. By 1 week and up to 3 weeks later expression is still seen in ≈66% of injured neurons, but the characteristic phenotypic switch in the subpopulations expressing BDNF occurs, whereby expression in the trkA population is reduced and expression in trkB- and in trkC-positive neurons is elevated. NGF infusion results in elevated levels of BDNF expression in both intact and injured trkA-positive neurons, accompanied by reduced trkB expression. NT-3 acts in an opposite fashion effecting a down-regulation in BDNF expression in intact neurons and preventing/reducing the injury-associated increases in BDNF expression in both trkC- and nontrkC-expressing subpopulations of injured neurons. These effects suggest NGF can regulate BDNF expression in trkA-expressing neurons regardless of the axonal state and that elevated levels of BDNF may contribute to the down-regulation in trkB expression associated with these states. Furthermore, the findings demonstrate that NT-3 can act in an antagonistic fashion to NGF in the regulation of BDNF expression in intact neurons, and mitigate BDNF's expression in injured neurons.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 5 (1993), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The peptide cholecystokinin (CCK) has been suggested to be involved in nociception, but its exact localization at the level of the spinal cord and in spinal ganglia has been a controversial issue. Therefore the distribution of messenger RNA (mRNA) for CCK was studied by in situ hybridization using oligonucleotide probes on sections of adult rat lumbar dorsal root ganglia following unilateral section of the sciatic nerve and on sections of untreated monkey trigeminal ganglia, spinal cord and spinal ganglia from all levels. For comparison, calcitonin gene-related peptide (CGRP) mRNA was also studied in the monkey tissue using the same techniques. Peripheral sectioning of the sciatic nerve in the rat resulted in the appearance of detectable CCK mRNA in up to 30% of remaining ipsilateral L4 and L5 dorsal root ganglion neurons 3 weeks after surgery, with a distinct but more limited appearance also in the contralateral ganglia. No cells, or only single cells, could be seen in normal control rat ganglia. In contrast, in the normal monkey, ∼20% of dorsal root ganglion neurons, regardless of spinal level, and 10% of trigeminal ganglia neurons expressed mRNA for CCK. CGRP mRNA was expressed at detectable levels in ∼80% of these monkey dorsal root ganglion neurons. In the monkey spinal cord, CCK mRNA was detected in the dorsal horn and in motoneurons, whereas CGRP mRNA was only seen in motoneurons. The present results suggest that CCK peptides can be involved in sensory processing in the dorsal horn of the spinal cord in normal monkeys and in rats after peripheral nerve injury, adding one more possible excitatory peptide to the group of mediators in the dorsal horn.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0167-0115
    Keywords: Coexistence ; Galanin ; Interaction ; Neuropeptide ; Primary sensory neuron ; Substance P
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Plasticity ; Enkephalin ; Vasoactive intestinal polypeptide ; Somatostatin ; Neuropeptide tyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The extent to which the plasticity in peptide expression observed in developing spinal motoneurons occurs following proximal peripheral axotomy in the adult rat was examined using in situ hybridization and immunohistochemical techniques to visualize the changes. Transient upregulation of galanin, vasoactive intestinal polypeptide (VIP) and substance P messenger ribonucleic acids (mRNAs) was observed within subpopulations of motoneurons ipsilateral to lesion for periods lasting 2–3 weeks after injury. In contrast, the axotomy-induced heterogenous increases in somatostatin and neuropeptide tyrosine mRNA expression in ipsilateral motoneurons remained elevated, or, in the case of somatostatin, continued to increase for the time period studied (1 month). Immunohistochemical analysis agreed with the in situ hybridization results, showing some motoneurons within the injured ventral horn to contain galanin-, VIP-or somatostatin-like immunoreactivity. In some instances, galanin-immunoreactive motoneurons colocalized with calcitonin gene-related peptide immunoreactivity. Most of the neurons expressing the injury-induced peptides appeared large, presumably alpha-motoneurons, but there were also many small neurons expressing galanin in the ventral horn ipsilateral to lesion. This may represent evidence for peptide synthesis in gamma-motoneurons. The only peptide mRNA studied to be downregulated in response to axotomy was enkephalin. The results show that peptide expression in injured motoneurons is dramatically altered, the significance of which remains to be determined.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1106
    Keywords: GAP-43 ; In situ hybridization ; Spinal cord ; Axotomy ; Rat ; Cat ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurocytology 15 (1986), S. 585-594 
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Injury of the peripheral axons of primary sensory neurons has been previously shown to increase the probability that the corresponding central axons would grow from the injured spinal cord into a peripheral nerve graft. This phenomenon has been used to investigate the nature of extrinsic cues from injured nerves that trigger an enhanced regenerative propensity within sensory neurons. In 13 groups of rats, a segment of the right sciatic nerve was grafted to the dorsal columns of the spinal cord and the left sciatic nerve was subjected to mechanical injury, injection of colchicine or infusion of nerve growth factor. Subsequently, neurons in lumbar dorsal root ganglia with axons growing from the spinal cord into a graft were identified by retrograde perikaryal labelling and compared for the two sides. The aim was to mimic or modify the inductive effect of nerve transaction by alternative or additional manipulation of the nerve. Growth of central axons was less enhanced by peripheral axonal interruption if the length of the proximal stump was increased or if a distal stump was present to permit rapid regeneration. However, the regenerative response following nerve transection was altered little by crushing the proximal stump or injecting it with colchicine or nerve growth factor. It is suggested that sensory neurons are stimulated to regenerate by peripheral axonal injuries that reduce some normal retrograde regulatory influence of Schwann cells.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Approximately one half of the neurons in the lumbar dorsal root ganglion of adult rats display high-affinity receptors for nerve growth factor (NGF). To ascertain which types of sensory neurons are potentially responsive to NGF, adjacent cryostat sections of rat dorsal root ganglia were processed either for NGF-receptor using radioautography or by one of four histochemical procedures. Histograms of the densities of neuronal labelling by radioiodinated NGF were examined for subpopulations of lumbar sensory neurons with thiamine monophosphatase enzyme activity or with immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, or somatostatin. Virtually all neurons with strong CGRP immunoreactivity had high-affinity NGF binding sites, although some neurons with faintly positive CGRP immunoreactivity lacked such NGF binding. A subpopulation of large neurons, approximately 5% of the total, had dense labelling by125I-NGF but were not stained by this immunohistochemical technique for CGRP. Of the three major populations of small neurons those with substance P immunoreactivity were consistently and heavily labelled by radioiodinated NGF whereas those with somatostatin immunoreactivity or thiamine monophosphatase activity were not specifically labelled by radioautography. For these primary sensory neurons in mature rats the genes for substance P and CGRP seem to be strongly expressed only in neurons capable of responding to NGF. On the other hand, neurons containing somatostatin and thiamine monophosphatase invariably lack high-affinity NGF receptors.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-6903
    Keywords: NGF receptors ; CNS cholinergic neurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In sections of rat forebrain, perikarya labeled radioautographically with125I-NGF resembled cholinesterase-positive neurons in their distribution within striatum and basal forebrain. Neurons with NGF receptors were also visualized in radioautographs prepared from the basal forebrain of a cerebrus monkey. Present techniques fail to detect axons projecting from basal forebrain to hippocampus or cortex which have been shown to take up NGF selectively in retrograde transport studies. In studies with membrane-enriched preparations from rat, high-affinity binding of125I-NGF (half maximal saturation in the 15–30 pM range) was detected in basal forebrain and striatum; lower levels of high-affinity binding were seen in hippocampus and neocortex. The binding and molecular properties of these receptors are similar to those described in other NGF-responsive tissues. These observations are further evidence supporting a biological role for NGF on some forebrain cholinergic neurons in adult rat.
    Type of Medium: Electronic Resource
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