TrkA immunoreactive neurones in the rat spinal cord

Abstract

We report the presence in rat spinal cord of a novel neuronal system expressing tyrosine kinase receptor (trkA), the high affinity receptor for nerve growth factor (NGF). TrkA immunoreactive cell bodies were observed in the intermediate grey matter of the spinal cord and were classified into three main groups: central canal cells located dorsolateral to the aqueduct, partition cells located between lamina X, and the lateral border of the intermediate grey, and a morphologically heterogeneous group which included large cells located near the lateral border. In situ hybridization confirmed that cells in all these areas express trkA mRNA. Combined immunofluorescence and retrograde Fluoro-Gold labelling was used to further characterise the projections and neurotransmitter profile of the trkA cells. Although often located in the vicinity of preganglionic cell groups, trkA immunoreactive cells are not themselves preganglionic. Rather, the central canal and partition cells belong to a neurochemically complex cholinergic propriospinal system. Many partition cells coexpress trkA, choline acetyltransferase (ChAT), the low affinity neurotrophin receptor, p75, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). In contrast, trkA immunoreactive central canal cells express ChAT, but do not express p75 and only a subpopulation express NADPH-d. The large trkA immunoreactive cells located on the lateral border do not express ChAT. TrkA immunoreactive fibres were also present and were located in the dorsal horn, in the dorsal columns, and in a bundle ventral to the aqueduct. However, double labelling revealed that the trkA immunoreactive fibres are not intrinsic but are primary afferent in origin and coexpress p75. The location of this novel trkA neuronal system is consistent with it having a role in the segmental integration of autonomic outflow. NGF could affect this system by modulating neuronal phenotype and/or synaptic efficacy.

Extensive Sprouting of Sensory Afferents and Hyperalgesia Induced by Conditional Expression of Nerve Growth Factor in the Adult Spinal Cord

“…Many of the CGRP-positive DRG neurons, in addition to trkA, also coexpress p75 (Wright and Snider, 1995;Michael et al, 1997b) and substance-P (Plenderleith et al, 1990). Therefore, it is not surprising that in our study CGRP-and SP-positive fibers would undergo collateral axonal growth in response to NGF.…”

Genetic Manipulation of Intraspinal Plasticity after Spinal Cord Injury Alters the Severity of Autonomic Dysreflexia

“…This implies that, in addition to sprouting of CGRP ϩ fibers, spinal cord injury most likely provokes NGF-independent reorganization of propriospinal pathways as well. On the other hand, the high-affinity NGF trkA receptor is located on cholinergic propriospinal neurons in the deep dorsal horn of the rat spinal cord (Michael et al, 1997), so the expansion of sacral-thoracic propriospinal projection may also be an NGF-dependent response to spinal injury. Such changes may provide a neural substrate for the amplification of discrete afferent signals (e.g., pressure sores, distended bladder or rectum), which elicit the synchronous discharge of sympathetic preganglionic neurons of the thoracic sympathetic chain, resulting in global sympathetic arousal including a potentially fatal hypertensive crisis.…”

Improved detection of fluorogold-labeled neurons in long-term studies

“…This method, using a light stable reaction product, has been used for easy assessment and detection of labeled neurons in short-term studies (Chang et al, 1990;Michael et al, 1997;Hoang et al, 2003). However, it is not known whether the use of an antibody against FG would help overcome the limitations associated with longer post-injection periods.…”