TRK and p75 neurotrophin receptor systems in the developing human brain

Abstract

The prenatal development of the neurons immunoreactive for high-affinity tropomycin-related kinase (trk) receptor (pan trk which recognizes trkA, trkB, and trkC) and low-affinity p75 neurotrophin receptor (p75NTR) was examined in the human brain from embryonic weeks 10 to 34 of gestation. In the embryonic week 10 specimen in which only brainstem regions were available for evaluation, trk immunoreactivity (trk-ir) was observed in the ventral cochlear, solitary, raphe, spinal trigeminal, and hypoglossal nuclei, as well as the vestibular complex and medullary reticular formation. At this time point of gestation, p75ntr-immunoreactive (p75NTR-ir) staining was observed within these same regions plus the inferior olivary and ambiguus nuclei. At embryonic week 14, trk-ir neurons were seen within the subplate zone of the entorhinal cortex, basal forebrain, caudate nucleus, putamen, external segment of the globus pallidus, specific thalamic nuclei, lateral mammillary nucleus, habenula nucleus, select brainstem nuclei, and the dentate nucleus of cerebellum. At this gestational time point, p75NTR-ir neurons were observed in each of these structures, with the exception of the caudate nucleus, specific thalamic nuclei, lateral mammillary nucleus, and habenula nucleus. Additionally, p75NTR-ir neurons were observed within the corpus callosum. The staining pattern for both trk and p75NTR remained unchanged at embryonic weeks 15 to 16 except for the addition of trk-ir and p75NTR-ir within the cortical subplate zone, hippocampus, and subthalamic nucleus. By embryonic week 18, trk-ir neurons were widely expressed within mostly all thalamic nuclei. In contrast, trk-ir was no longer seen within the hypoglossal, cuneate, and gracile nuclei at this time point. This staining pattern for trk and p75NTR remained virtually unchanged from embryonic weeks 19 to 20 and embryonic weeks 16 to 20, respectively. From embryonic weeks 22 to 34, the distribution of both trk-ir and p75NTR-ir neurons changed gradually. During this period, neurons in most thalamic and some brainstem nuclei became progressively immunonegative for trk, whereas neurons in the neocortical subplate zone, corpus callosum, and hilar region of dentate gyrus gradually lost immunoreactivity for p75NTR. These data demonstrate an important and complex role for both the high-(trk) and low- (p75) affinity neurotrophin receptors during the development of multiple neuronal systems in the human brain.

Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan

“…In layer 1, trkB TK+ mRNA-positive cells were observed throughout the postnatal life of humans. While the identity of the trkB TK+ mRNA-positive cells found in the human subcortical white matter or in layer I was not determined in our study, other groups have demonstrated that subplate neurons and layer I Cajal-Retzius (CR) cells express trkB in rodent brain, and that subplate neurons express pan-trk in the developing human brain (Cabelli et al, 1996;Chen et al, 1996;Fukumitsu et al, 1998;Ringstedt et al, 1998). Recent evidence suggests that CR cells continue to exist in the adult human prefrontal cortex (Martin et al, 1999).…”

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

“…In particular, ChAT-positive, p75-negative neurons have been reported in the nucleus basalis-substantia innominata complex, whose fibers have been surmised to project to the amygdala and parts of the rhinal paralimbic areas (Heckers et al 1994). An absence or decrease in the p75 receptor has been demonstrated in the amygdala of rodents (Yan and Johnson 1988) as well as in the entorhinal cortex of humans (Kordower and Mufson 1992;Chen et al 1996). This may explain the relative sparing of ChAT observed in immunotoxintreated animals in the entorhinal-piriform cortex and the amygdala (Heckers et al 1994;Schliebs et al 1996).…”

Deafferentation and neurotrophin‐mediated intraspinal sprouting: a central role for the p75 neurotrophin receptor

“…It is known that CGRP-expressing primary afferent neurons, serotonergic neurons in the Raphe nuclei, noradrenergic neurons of the locus ceruleus and dopaminergic neurons of the hypothalamus all express p75 in several species, including humans (Sobreviela et al, 1994;Berg-von der Emde et al, 1995;Wright & Snider, 1995;Chen et al, 1996;Yamuy et al, 2000), implicating a possible direct role for p75 NTR in suppressing spinal plasticity. TH-expressing axons in the substantia nigra pars compacta, some of which also project spinally, do not express p75 NTR (Chaisuksunt et al, 2003) so, if these axons sprout after rhizotomy and ⁄ or neurotrophic factor treatment, the underlying mechanism is likely to be p75 NTR independent.…”

“…The present results represent the first report of decreased spinal innervation by descending monoaminergic axons in p75-⁄ -mice. While these axonal phenotypes are known to express p75 NTR (Sobreviela et al, 1994;Berg-von der Emde et al, 1995;Chen et al, 1996;Yamuy et al, 2000), it remains unknown whether the decrease in spinal axon density is due to a developmental decrease in neuronal number and ⁄ or to a decrease in spinal branching.…”