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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Activating transcription factor-3 (ATF3) is a member of the ATF/CREB transcription factor superfamily and is induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study the regulation of ATF3, we have examined the effect of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on ATF3 expression. In untreated rats, sciatic nerve transection induced ATF3 immunoreactivity in 82% of L4 DRG cells at 14 days after axotomy. Intrathecal delivery of NGF or GDNF for 2 weeks commencing immediately after injury reduced the ATF3 expression to 35 and 23% of DRG cells, respectively. Cell size analysis indicated that NGF had protected a population of mainly small- to medium-sized cells, but that the GDNF had protected a population of both small and large cells. This effect was confirmed by double labelling for P2X3, CGRP and 200 kDa neurofilament, markers for small peptide-poor cells, peptide-rich cells and large cells, respectively. Thus GDNF reduced the percentage of ATF3-immunoreactive P2X3 cells from 70 to 4%, and the percentage of ATF3-immunoreactive neurofilament cells from 63 to 24%. NGF was less effective than GDNF in reducing ATF3 expression in these cell types, but reduced the percentage of ATF3-immunoreactive CGRP cells from 10% to 〈 1%. These results show that ATF3 expression in specific populations of DRG cells can be modulated by exogenous supplementation of specific trophic factors, and suggest that ATF3 expression may normally be induced by the loss of target-derived NGF and GDNF.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have shown that following neonatal peripheral nerve injury, adjacent intact myelinated and unmyelinated primary afferents sprout into the central denervated terminal area. The present study investigates this in more detail and goes further, to study the fate of the central terminals of the surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B-HRP), to label the A fibres, or wheatgerm agglutinin (WGA-HRP), to label C fibres were employed to investigate the central consequences of sciatic nerve section and ligation on the day of birth, in adult rats. Bulk labelling of the axotomized sciatic or intact saphenous nerve with either tracer and comparison with contralateral controls revealed alterations to the terminal field. The intact saphenous nerve terminal field expanded caudally from mid L4 to the L4-L5 boundary when labelled with WGA-HRP and to the sacral cord when labelled with B-HRP. Labelling the axotomized sciatic nerve with either tracer revealed little change in the overall somatotopic organization of central terminals, although labelling was less intense compared to control nerves and more variable with WGA-HRP. Invasion of the substantia gelatinosa (SG) by axotomized A fibres was observed in segments L3-5, into the area occupied by axotomized C fibres. This area was also invaded by intact saphenous A fibres in the L4–5 segments. These results demonstrate that following neonatal nerve section: (i) axotomized primary afferents are able to retain a ‘normal’ somatotopic map in the rostrocaudal plane; (ii) both A and C fibres from adjacent intact nerves sprout into the denervated territory, but A fibres sprout further caudally; (iii) axotomized A fibres and invading intact A fibres both sprout dorsally into denervated SG. As a result, there is considerable overlap between nerve territories in denervated spinal cord, suggesting that competition for laminar termination sites exists between A and C fibres and also between axotomized and intact primary afferents.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 3 (1991), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The rostrocaudal distribution of saphenous nerve inputs into the lumbar dorsal horn from L2 to L6 has been investigated in urethane anaesthetized rats whose left sciatic nerve was cut and ligated at birth. In normal cord, electrical stimulation of the saphenous nerve evoked dorsal horn spikes in L2 to caudal L4. Few or no spikes were evoked in L5. After neonatal sciatic nerve section, saphenous nerve stimulation evoked spikes throughout segments L2 to L6. Dorsal horn cell receptive fields were also altered following neonatal sciatic nerve section. A somatotopic map of the lumbar enlargement in normal rats was constructed from the receptive fields (RFs) of adjacent dorsal horn cells. Cells with RFs in the saphenous skin region were concentrated in L3 and rostral L4 and very few were found in L5. After neonatal sciatic nerve section, however, a substantial number of cells with low threshold saphenous skin RFs were also found in caudal L4 and throughout L5. These results show that the central saphenous nerve terminal sprouts that grow into the sciatic terminal region following neonatal sciatic nerve section (Fitzgerald, 1985, J. Comp. Neurol., 240, 414–422; Fitzgerald et al., 1990, J. Comp. Neurol., 300, 370–385) form functional connections. This results in dorsal horn cells that are not normally influenced by saphenous nerve inputs developing substantial low threshold RFs in saphenous nerve skin regions.
    Type of Medium: Electronic Resource
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  • 4
    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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