TrkA, trkB, and trkC messenger RNA expression by bulbospinal cells of the rat
Section snippets
Animal surgery
All experimental procedures described below were carried out in accordance with the U.K. Animals Act of 1986. To retrogradely label bulbospinal pathways, adult male Wistar rats (Charles River, U.K., 200–300 g) were anesthetized with sodium pentobarbital (Sagatal, RMB, 60 mg/kg). A laminectomy was performed over either the upper cervical (n=3) or midthoracic (n=2) spinal cord. A small amount of tissue was removed on the dorsal aspect of the cord and a piece of gelfoam soaked in 10 μl of FluoroGold
Distribution of FluoroGold-labelled cells
FluoroGold labelling was present in neurons of most of the brainstem areas previously reported to have spinal projections.15 All animals had numerous FluoroGold-labelled cells in the reticular portion of the pons (Fig. 1a, d, f, h), raphe magnus (Fig. 2g, i), raphe pallidus, vestibular nucleus, subcoeruleus, and red nucleus (Fig. 3d, f). All animals also had FluoroGold-labelled cells in the raphe obscurus and the A5 nucleus (Fig. 2a). Labelling in the locus coeruleus was more variable with two
Discussion
The results of the present study show that both trkB and trkC mRNA expression occurs on the vast majority of bulbospinal neurons. It could be argued that the surgical procedures used induced some of this expression. However, we and other investigators20., 29., 31. have noted that similar extensive trkB and trkC expression occurs in the brainstem of normal unoperated animals. In the case of bulbospinal cells, it could be argued that our criteria of determining whether a cell was expressing trkB
Conclusions
Taken together, these results suggest that the expression of high-affinity neurotrophin receptors is an important facet in determining the responsiveness of bulbospinal neurons to neurotrophin treatment. Virtually all bulbospinal neurons express trkB and trkC and may therefore be amenable to treatment with BDNF, NT-4/5, and NT-3. However, the levels of trk receptors vary and other factors also contribute to the effects of neurotrophins on cell survival and/or axonal regeneration.
Acknowledgements
This work was supported by the Medical Research Council (U.K.) and St Thomas's Hospital Research Endowments. Dr T. Görcs is gratefully thanked for provision of the rabbit 5-HT antibody.
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2014, PainCitation Excerpt :These results suggest that time course, location, and degree of noradrenergic neuroplasticity after nerve injury would depend on the type of nerve injury. Unlike postganglionic sympathetic noradrenergic neurons, which express tropomyosine receptor kinase A (trkA) and respond to nerve growth factor, noradrenergic neurons in the LC express trkB and respond to brain-derived neurotrophic factor (BDNF) [14]. As peripheral nerve injury up-regulates the expression of BDNF to increase noradrenergic axon density in the spinal cord, and as a local injection of BDNF into the spinal dorsal horn increases noradrenergic axon density in normal rats [12], one could argue that local up-regulation of BDNF after peripheral nerve injury increases noradrenergic tone in the PFC. However, animals and humans with depression, which is often concomitant with chronic pain, show lower rather than higher levels of BDNF in the PFC compared to normal subjects [22,25].
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2012, Experimental NeurologyCitation Excerpt :Thus, peptidergic nociceptive neurons are sensitive to NGF, and mechanoreceptive neurons, to NT-3. Descending serotonergic, dopaminergic, and noradrenergic neurons express TrkB and TrkC (King et al., 1999; Loudes et al., 1999) and can be encouraged to regenerate with BDNF and NT-3 treatment following SCI (Bregman et al., 1997). Serotonergic, noradrenergic, and hypothalamic dopaminergic neurons all express p75 in several species, including humans (Sobreviela et al., 1994; Berg-von der et al., 1995; Wright and Snider, 1995; Chen et al., 1996; Yamuy et al., 2000).
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2012, Handbook of Clinical NeurologyCitation Excerpt :Its full-length receptor (TrkB) is expressed by most populations of descending supraspinal axons (Klein et al., 1989, 1990) and by ∼ 95% of ascending spinal projection neurons (Bradbury et al., 1998). BDNF promotes regeneration of injured corticospinal (Jin et al., 2002; Sasaki et al., 2009), rubrospinal (Liu et al., 1999), vestibulospinal (Jin et al., 2002), reticulospinal (Jin et al., 2002), monoaminergic (King et al., 1999), and sensory axons (Oudega and Hagg, 1999). In addition, BDNF treatment reverses neuronal atrophy (Giehl and Tetzlaff, 1996; Kobayashi et al., 1997; Kwon et al., 2002, 2007; Liu et al., 2002) and causes sprouting of uninjured descending serotonergic axons and intrinsic GABAergic interneurons (Ramer et al., 2007; Soril et al., 2008).