Glial cell line derived neurotrophic factor (GDNF) regulates VR1 and substance P in cultured sensory neurons

Ogun-muyiwa, Patrick; Helliwell, Rachel J. A.; McIntyre, Peter; Winter, Janet

doi:10.1097/00001756-199907130-00021

Cited by 75 publications

(51 citation statements)

References 5 publications

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“…It is reported that GDNF may contribute to the regulation of nociceptive properties in cultured sensory neurons [Ogun-Muyiwa et al, 1999]. Thus, GDNF and BDNF may be involved in the nociceptive neurotransmission at lamina I to II of the spinal dorsal horn to which DRG neurons project centripetal axon terminals.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal

Ohta

Inokuchi

Gen

et al. 2001

Cells Tissues Organs

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The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic substance in the central and peripheral nervous systems. The present immunohistochemical study clarified the ultrastructural localization of GDNF-immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerve stumps and also at normal spinal dorsal horn, and has demonstrated that GDNF-IR products appear to be located in dense-cored vesicles within the axons. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligation maneuver involving the sciatic nerve. In the early period after the ligation (20 h), GDNF-IR fibers were observed in the proximal and distal segment of the ligations, but no immunoreactivities were detected in the middle segment. On the other hand, at a late period (8 days) after the transection, GDNF-IR fibers had almost disappeared, but weak GDNF-IR was observed in Schwann cells in the proximal and distal stumps of transected nerve. These findings suggest that most of GDNF-IR was transported from the proximal or distal side in the early period, but was locally synthesized by Schwann cells around the ligations in the late period. Spinal rhizotomy caused prominent accumulation of GDNF-IR products at the cut end of the ganglion side of the dorsal root, but not at the ventral root. These results suggested that dorsal root ganglionic (DRG) sensory neurons are one of the origins of GDNF. The fact that small- to medium-sized DRG neurons show enhanced GDNR-IR after the colchicine treatment may support the above suggestion. In conclusion, the present results strongly suggest that a subgroup of DRG sensory neurons synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon terminals.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal

Ohta

Inokuchi

Gen

et al. 2001

Cells Tissues Organs

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“…In addition to posttranslational regulation, NGF might regulate TRPV1 mRNA levels. Over extended culture periods (3-10 days) of DRG neurons from adult rats, NGF can maintain higher numbers of TRPV1-mRNApositive and TRPV1-immunoreactive cells (Ogun-Muyiwa et al 1999;Bron et al 2003) and increase TRPV1 mRNA levels in comparison with controls as found by Northern Blot (Winston et al 2001). NGF also prevents the decline in the number of cold-sensitive DRG neurons with time in culture as analysed via the cold-induced elevation of intracellular calcium concentration (Babes et al 2004).…”

Section: Ngf Is Involved In Embryonic Regulation Of Trp Channel Exprementioning

confidence: 96%

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

2009

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Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of nonpeptidergic nociceptors is also promoted by the NGFsignalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.

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“…Second, the density of sympathetic sprouts in the DRG does not correlate with neuropathic pain intensity (8). Given that 1) DRG neurons express receptors for satellite cell-derived proinflammatory cytokines and growth factors (204,216) and 2) these proinflammatory cytokines and growth factors act in a paracrine fashion to influence large numbers of cells, perhaps it may be that these satellite cell-derived substances are really the basis for altered pain, rather than the sympathetic sprouts. From this perspective, sympathetic sprouting into DRGs may simply be a "side effect" of glial activation.…”

Section: C) Implications Of Sympathetic Nervous System Involvementmentioning

confidence: 99%

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

Watkins

Maier

2002

Physiological Reviews

653

433

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Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.

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Glial cell line derived neurotrophic factor (GDNF) regulates VR1 and substance P in cultured sensory neurons

Cited by 75 publications

References 5 publications

Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal

Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

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