Elsevier

Neuroscience

Volume 92, Issue 3, June 1999, Pages 935-944
Neuroscience

TrkA, trkB, and trkC messenger RNA expression by bulbospinal cells of the rat

https://doi.org/10.1016/S0306-4522(99)00072-XGet rights and content

Abstract

Previous research has shown that corticospinal as well as rubrospinal neurons express the high-affinity trkB and trkC receptors but not the high-affinity trkA receptor. To determine if bulbospinal neurons in other brainstem areas show the same pattern of trk receptor expression, bulbospinal cells were labelled via the injection of the retrograde tracer FluoroGold into the spinal cord. Brainstem sections were then processed for in situ hybridization using oligonucleotide probes to the trkA, trkB, and trkC receptors. The results indicated that, although trkA expression occurred in brainstem areas that contain bulbospinal neurons (e.g., the vestibular nuclei, and the pontine reticular formation), very few FluoroGold-labelled cells expressed the trkA receptor. In contrast, at least 90% of bulbospinal cells in each brainstem area examined expressed the trkB receptor. Quantitative analysis indicated differences in the level of trkB labelling between bulbospinal cells in different brainstem areas, with the highest levels seen in the locus coeruleus and magnocellular portion of the red nucleus, and the lowest levels seen in the medial and superior vestibular nuclei and the raphe obscurus. With the exception of the accessory trigeminal nucleus, over 84% of bulbospinal cells in each brainstem area also expressed the trkC receptor. TrkC receptor expression was greatest in the locus coeruleus and subcoeruleus and lowest in the accessory trigeminal nucleus, the raphe magnus, and the vestibular nuclei.

Results indicate that, as with other descending pathways, virtually all bulbospinal pathways should be amenable to treatment with brain-derived neurotrophic factor, neurotrophin-4/5 or neurotrophin-3, but not nerve growth factor, following spinal cord damage.

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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