Coexpression of trk family members and low-affinity neurotrophin receptors in rat dorsal root ganglion neurons

Kashiba, Hitoshi; Noguchi, Koichi; Ueda, Yoshihiko; Senba, Emiko

doi:10.1016/0169-328x(94)00249-e

Cited by 76 publications

(55 citation statements)

References 21 publications

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“…tent with previously published data (Averill et al, 1995;Bennett et al, 1996). The similarity in previously published percentages of positive neurons (35-40%) (Averill et al, 1995;Kashiba et al, 1995) to our strongly stained neurons (37%) suggests that these investigators used criteria for defining trkAϩ staining that are close to 40% intensity (strongly positive in our study), a level that we find is selective for nociceptive somatic afferent neurons (see below). Thus, neurons in the present study with weak but positive trkA staining may not be classed as positive by other groups.…”

Section: Resultssupporting

confidence: 79%

trkA Is Expressed in Nociceptive Neurons and Influences Electrophysiological Properties via Nav1.8 Expression in Rapidly Conducting Nociceptors

Fang¹,

Djouhri²,

McMullan³

et al. 2005

J. Neurosci.

134

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To test the hypothesis that trkA (the high-affinity NGF receptor) is selectively expressed in nociceptive dorsal root ganglion (DRG) neurons, we examined the intensity of trkA immunoreactivity in single dye-injected rat DRG neurons, the sensory receptor properties of which were identified in vivo with mechanical and thermal stimuli. We provide the first evidence in single identified neurons that strong trkA expression in DRGs is restricted to nociceptive neurons, probably accounting for the profound influence of NGF on these neurons. Furthermore, we demonstrate that trkA expression is as high in rapidly conducting (A␣/␤) as in more slowly conducting (A␦ and C) nociceptors. All A␣/␤ low-threshold mechanoreceptors (LTMs) are trkA negative, although weak but detectable trkA is present in some C and A␦ LTMs.NGF can influence electrophysiological properties of DRG neurons, probably by binding to trkA. We found positive correlations for single identified A␣/␤ (but not C or A␦) nociceptors between trkA immunocytochemical intensity and electrophysiological properties typical of nociceptors, namely long action potential and afterhyperpolarization durations and large action potential amplitudes. Furthermore, for A␣/␤ (not C or A␦) nociceptors, trkA intensity is inversely correlated with conduction velocity. Similar relationships, again only in A␣/␤ nociceptors, between electrophysiological properties and trkA expression exist for sodium channel Nav1.8 but not Nav1.9 immunoreactivities. These findings suggest that in A␣/␤ nociceptors, influences of NGF on expression levels of Nav1.8 are related to, and perhaps limited by, expression levels of trkA. This view is supported by a positive correlation between immuno-intensities of trkA and Nav1.8 in A-fiber, but not C-fiber, nociceptors.

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Section: Resultssupporting

confidence: 79%

trkA Is Expressed in Nociceptive Neurons and Influences Electrophysiological Properties via Nav1.8 Expression in Rapidly Conducting Nociceptors

Fang¹,

Djouhri²,

McMullan³

et al. 2005

J. Neurosci.

134

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“…We also cannot exclude the possibility that some BDNF cells express trkB at levels below our detection threshold. Consistent with other recent studies (Kashiba et al, 1995;Wright and Snider, 1995;McMahon et al, 1997), we observed minimal overlap between trkA and trkB cells (Fig. 10).…”

Section: Drg Subgroups That Synthesize Bdnfsupporting

confidence: 82%

“…All three trks are expressed within adult dorsal root ganglia (McMahon et al,1994;Kashiba et al, 1995;Wright and Snider, 1995), and all members of the neurotrophin family show retrograde transport to dorsal root ganglia from peripheral nerves (DiStefano et al, 1992;Curtis et al, 1995). BDN F, however, is unusual in being also produced by adult dorsal root ganglion (DRG) cells (Ernfors et al, 1990(Ernfors et al, , 1993Wetmore and Olson, 1995;Apfel al., 1996;Cho et al, 1997), although the role of this BDN F is not known.…”

Section: Abstract: Brain-derived Neurotrophic Factor; Mrna; Trka; Trmentioning

confidence: 99%

Nerve Growth Factor Treatment Increases Brain-Derived Neurotrophic Factor Selectively in TrkA-Expressing Dorsal Root Ganglion Cells and in Their Central Terminations within the Spinal Cord

Michael

Averill

Nitkunan³

et al. 1997

J. Neurosci.

485

380

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Using immunocytochemistry and in situ hybridization, we have examined the expression of brain-derived neurotrophic factor (BDNF) and of neurotrophin receptors in dorsal root ganglion cells. In the adult rat, BDNF mRNA and protein were found mainly in the subpopulation of cells that express the nerve growth factor (NGF) receptor trkA and the neuropeptide calcitonin gene-related peptide (CGRP). NGF increased BDNF within the trkA/CGRP cells to the extent that almost 90% of trkA cells contained BDNF mRNA after intrathecal NGF treatment, and 80-90% of BDNF-expressing cells contained trkA. Non-trkA cells that expressed BDNF included some trkC cells and some small cells that labeled with the lectin Griffonia simplicifolia IB4, a marker for cells that do not express trks. However, very few trkB cells expressed either BDNF mRNA or protein, and NGF did not increase BDNF expression in non-trkA cells. BDNF protein was anterogradely transported both peripherally and centrally. The central transport resulted in BDNF immunoreactivity in CGRP containing terminal arbors in the dorsal horn of the spinal cord, and this immunoreactivity was increased by NGF treatment. Electron microscopic analysis revealed that the BDNF immunoreactivity was present in finely myelinated and unmyelinated axons and in axon terminals, where it was most concentrated over dense-cored vesicles.Our data do not support an autocrine or paracrine role for BDNF within normal dorsal root ganglia, but indicate that BDNF may act as an anterograde trophic messenger. NGF levels in the periphery could influence dorsal horn neurons via release of BDNF from primary afferents.

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“…The receptor responsible for the NT4-dependent survival of D-hair receptors is most likely trkB, because D-hair receptors survive in normal proportions in mice lacking the low-affinity p75 receptor . Furthermore, because trkB is expressed by 10 -20% of dorsal root ganglion neurons, most of which have medium to large somata that give rise to myelinated axons (Kashiba et al, 1995;Wetmore and Olson, 1995;Wright and Snider, 1995), the population of sensory neurons that expresses trkB correlates with the population likely to be D-hair receptors. Although p75 is not required for the survival of D-hair receptors, the presence of p75 is necessary for the normal mechanical f unction of D-hairs, because D-hair receptors in p75Ϫ/Ϫ mice are impaired in mechanical f unction .…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin 4 Is Required for the Survival of a Subclass of Hair Follicle Receptors

et al. 1998

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Neurotrophin-4 (NT4) is the most recently discovered neurotrophic factor in mammals and, functionally, the least well understood. Here, we used mice that lack NT4 to determine whether NT4 is required for the survival of functionally identified subclasses of cutaneous sensory neurons. By using three independent methods of histological and electrophysiological analysis, we show that NT4 is specifically required for the survival of down hair (D-hair) receptors that innervate a subpopulation of hair follicles. All other functionally distinct types of afferents neurons innervating hairy skin were not affected in their survival or in their function. Previous studies have shown that BDNF is required for the mechanical sensitivity of slowly adapting (SA) mechanoreceptors but not for the postnatal survival of myelinated cutaneous afferent fibers. In contrast, the receptive properties of SA mechanoreceptors were not impaired in animals lacking NT4. Consequently, these data show that the two trkB ligands, NT4 and BDNF, have distinct and nonoverlapping roles in supporting cutaneous sensory neurons. Whereas NT4 is required for the survival of D-hair receptors, BDNF supports the mechanical function of SA fibers.

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Coexpression of trk family members and low-affinity neurotrophin receptors in rat dorsal root ganglion neurons

Cited by 76 publications

References 21 publications

trkA Is Expressed in Nociceptive Neurons and Influences Electrophysiological Properties via Nav1.8 Expression in Rapidly Conducting Nociceptors

trkA Is Expressed in Nociceptive Neurons and Influences Electrophysiological Properties via Nav1.8 Expression in Rapidly Conducting Nociceptors

Nerve Growth Factor Treatment Increases Brain-Derived Neurotrophic Factor Selectively in TrkA-Expressing Dorsal Root Ganglion Cells and in Their Central Terminations within the Spinal Cord

Neurotrophin 4 Is Required for the Survival of a Subclass of Hair Follicle Receptors

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