Differential Expression of the p75 Nerve Growth Factor Receptor in Glia and Neurons of the Rat Dorsal Root Ganglia after Peripheral Nerve Transection (original) (raw)
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The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Sympathetic nerve terminals on blood vessels within the dorsal root ganglia sprout after sciatic nerve lesions in the rat. The mechanism underlying this phenomenon is not clear, but might be predicted to involve nerve growth factor or its homologs because these factors are known to trigger collateral sprouting of undamaged sympathetic noradrenergic terminals. We have found that sciatic nerve lesions lead to a decreased expression of neuronal p75, the low-affinity receptor for the neurotrophins, but an increased expression of glial p75 in ipsilateral dorsal root ganglia. Intriguingly, the increased expression of p75 was found primarily in association with glia surrounding large-diameter neurons, which are those associated with the noradrenergic sprouts. A smaller but significant glial response was also found in contralateral ganglia. The glial response in ipsilateral ganglia could be mimicked by ventral, but not dorsal, root transection. The dorsal root lesion-induced glial responses...
Journal of neurocytology, 1999
Tyrosine hydroxylase immunocytochemistry was used to reveal the sympathetic postganglionic axons that sprout to form basket-like skeins around the somata of some primary sensory neurons in dorsal root ganglia (DRGs) following sciatic nerve injury. Ultrastructural observations in rats revealed that these sprouts grow on the surface of glial lamellae that form on the neurons. Sciatic nerve injury triggers glial cell proliferation in the DRG, and the formation of multilamellar pericellular onion bulb sheaths, primarily around large diameter DRG neurons. We infer that these glia participate in the sprouting process by releasing neurotrophins and expressing growth supportive cell surface molecules. Many DRG cell somata, and their axons in intact nerves and nerve end neuromas, express alpha2A adrenoreceptors intracytoplasmically and on their membrane surface. However, sympathetic axons never make direct contacts with the soma membrane. The functional coupling known to occur between sympat...
Neuroscience Letters, 1997
Following sciatic nerve injury, sympathetic axons sprout into the L5 dorsal root ganglion (DRG). The low-affinity neurotrophin receptor (p75) is strongly expressed by glial cells in DRG following axotomy. We tested the hypothesis that p75 is involved in this sympathetic sprouting by comparing sprouting following sciatic nerve cut in wild-type (CD1) and p75 knockout mice. Twenty-one days after injury sympathetic sprouting had occurred in both mouse strains, though the extent of sprouting (measured as length of sprouts per unit area of DRG) was less in p75 knockout mice. We conclude that p75 expression enhances, but is not required for, sympathetic sprouting. © 1997 Elsevier Science Ireland Ltd.
European Journal of Neuroscience, 1999
Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known. Using in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin-3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Quantitative analysis showed that the levels of mRNAs for NT3 and NGF increased in ipsilateral but not contralateral DRG after nerve injury. Noradrenergic sprouting around the axotomized neurons was associated with p75-immunoreactive satellite cells. Further, antibodies specific to NGF or NT3, delivered by an osmotic mini-pump to the DRG via the lesioned L5 spinal nerve, significantly reduced noradrenergic sprouting. These results implicate satellite cell-derived neurotrophins in the induction of sympathetic sprouting following peripheral nerve injury.
Pain, 1997
We compared the time-course of sympathetic nerve sprouting into the L4-6 dorsal root ganglia (DRG) of adult rats following a chronic constriction injury (CCI) made on the sciatic nerve, or following sciatic nerve transection at the same site. We also tested the rats for changes in threshold for withdrawal from mechanical and thermal stimuli delivered to the hindpaws. We found sympathetic sprouting in DRG by 4 days following CCI, paralleling the decreases in mechanosensory threshold and preceding changes in thermal thresholds. However, with sciatic nerve transection, sympathetic sprouting was not detectable until 14 days after nerve injury. Thus, after CCI, sympathetic sprouting occurs with a sufficiently rapid time-course for it to play a role in the genesis of neuropathic pain. We suggest that the more rapid sprouting seen after CCI than after resection is due to the availability of products of Wallerian degeneration, including nerve growth factor, to both spared and regenerating axons following CCI, but not following resection. © 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
Neuroscience Letters, 1996
Peripheral nerve injury often induces sympathetic nerve fiber sprouting in the dorsal root ganglion (DRG) and injured nerve. Presently, the underlying mechanism and functional significance of the sprouting are unknown. This study was performed to see whether the degree of the sprouting in the DRG was a function of the distance between the DRG and injury site. To this aim, we compared two groups of rats with respect to the sympathetic nerve fibers sprouting in the S1-3 DRG; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the 3and3 and 3and4 spinal nerves ($34 group) and the other group at the levels between the S1 and 2,between2, between 2,between2 and 3andbetween3 and between 3andbetween3 and 4spinalnerves(S123group).ThetransectionsinbothgroupsequallyeliminatedtheinputsfromthetailtotheS1−3DRG,butthedistancefromtheS1/4 spinal nerves (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/4spinalnerves(S123group).ThetransectionsinbothgroupsequallyeliminatedtheinputsfromthetailtotheS1−3DRG,butthedistancefromtheS1/2 DRG to the injury site was different between the two groups. Immunohistochemical staining with tyrosine hydroxylase (TH) antibody of the S 1-3 DRG removed from rats a week after the injury revealed that the degree of penetration of TH-positive fibers into the S 1 and 2DRGwasmuchmoreextensiveintheS123groupthaninthe2 DRG was much more extensive in the S 123 group than in the 2DRGwasmuchmoreextensiveintheS123groupthaninthe34 group, whereas that into the $3 DRG was not significantly different between the two groups. These results suggest that the extent of the sympathetic nerve fiber sprouting in the DRG following peripheral nerve injury is inversely related to the distance between the DRG and injury site.
Neuroscience Letters, 1999
Partial peripheral nerve injury often results in neuropathic pain that is aggravated by sympathetic excitation and induces sympathetic nerve sprouting in both the injured nerve and corresponding dorsal root ganglia (DRGs). Presently, the functional mechanisms of the interactions between the sprouting and injured somatic afferents remain uncertain. This study was performed to see whether the sprouting in the DRGs plays a key role in the development of neuropathic pain. To this aim, we compared two groups of rats, both of which were subjected to unilateral transection of the superior and inferior caudal trunks at the level between the S1 and S2 spinal nerves, with respect to sympathetic ®ber sprouting; one group showed well-developed neuropathic pain behaviors (i.e. mechanical, cold and warm allodynia signs) and the other group showed poorly-developed ones. Immuno-histochemical staining with tyrosine hydroxylase (TH) antibody of the injured S1 DRG taken from both groups of rats after behavioral tests revealed that the magnitude of penetration of TH-positive ®bers into the S1 DRG was not signi®cantly different between the two groups. These results suggest that sympathetic nerve sprouting in the injured DRG is not a key factor in the development of neuropathic pain.
Role of nerve growth factor in the adult dorsal root ganglia neuron and its response to injury
The Journal of Comparative Neurology, 1984
The response of dorsal root ganglia (DRG) neurons to NGF deprivation and to axotomy was examined in adult guinea pigs. The success of NGF deprivation by means of an autoimmune approach was monitored by the measurement of serum antibody titer levels against guinea pig NGF with the standard bioassay for NGF activity. That the antibody produced NGF deprivation was confirmed by histologic evidence of neuronal atrophy and apparent cell loss in sections of the superior cervical ganglia (SCG) and by marked decreases (65-80%) of SCG neurotransmitter-synthesizing enzyme activity levels. By using the autoimmune approach a new source of guinea pigs was found which consistently produced high titers of cross-reacting anti-NGF antibodies. Experiments were designed to examine the response of the sensory neuron to injury while chronically deprived of NGF. Total neuronal counts in the sixth lumbar DRG 98 days after sciatic nerve crush showed no difference between NGF-deprived and control ganglia. Measurement of the size spectrum of DRG neurons showed evidence of atrophy of the NGFdeprived neurons in both the uninjured and axotomized side compared to respective controls. The mean volume of uninjured sensory neurons measured in the NGF-deprived guinea pigs was decreased 27.7% (P < .05) compared with that of control guinea pigs. The degree of regeneration 6 days following a nerve crush was the same in NGF-deprived sensory neurons and in controls when measured by the "pinch test" and by isotope-labeled axonal transport studies. The long-term regenerative response was analyzed with various histologic and morphometric techniques studying the sural nerve 98 days after sciatic nerve crush. No differences between control and NGF-deprived guinea pig sural nerves were noted at the light microscopic and ultrastructural levels. These studies demonstrated an unimpaired regenerative capability of sensory neurons deprived of NGF compared with controls.
Neuroscience Letters, 1998
Incomplete peripheral nerve injury often leads to neuropathic pains, some of which are relieved by sympathectomy, and results in sympathetic postganglionic nerve fiber sprouting in the dorsal root ganglion (DRG). This study was performed to see whether the sprouting in the DRG plays a key role in the sympathetic dependence of neuropathic pain. To this aim, we compared two groups of rats, both of which were subjected to unilateral transection of the inferior and superior caudal trunks at the levels between the S1 and S2, S2 and S3, and S3 and S4 spinal nerves, with respect to sympathetic fiber sprouting; one group showed neuropathic pain behaviours (i.e. mechanical and cold allodynia signs) which were very sensitive to phentolamine, alpha adrenergic blocker, and the other group exhibited no sensitivity. Immuno-histochemical staining with tyrosine hydroxylase antibody of the S1-S3 DRGs was not correlated with the sensitivity to phentolamine. These results suggest that the degree of sympathetic dependence of neuropathic pain is not a function of the extent of the sympathetic postganglionic nerve fiber sprouting in the DRG.
Experimental Brain Research, 1997
The time course of the astroglial cell reaction in the nucleus gracilis and the spinal cord dorsal horn was examined following sciatic nerve transection in the adult rat with qualitative and quantitative analysis of glial fibrillary acidic protein immunoreactivity and in situ hybridization for its mRNA. In addition, the potential effect of exogenous nerve growth factor (NGF) was examined on the astroglial and microglial cells in the spinal cord dorsal horn at certain time points following sciatic nerve transection. An increase in glial fibrillary acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day after lesioning, with a peak at about 1 week and 2 days after lesioning, respectively, followed by a decline. However, NGF application during 1, 2 and 4 weeks following nerve transection did not result in any significantly reduced astroglial or microglial activity. Our results show that the astroglial cell response in the nucleus gracilis and the spinal cord dorsal horn is rapid in comparison with previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration), that the astroglial cell reaction develops concomitantly with the microglial cell reaction previously described and that the "signal" from the axotomized neurons which induces these reactions can not be prevented by exogenous NGF applied to the peripheral nerve.