TRK and p75 neurotrophin receptor systems in the developing human brain

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 (p75(NTR)) 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, p75(NTR)-immunoreactive (p75(NTR)-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, p75(NTR)-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, p75(NTR)-ir neurons were observed within the corpus callosum. The staining pattern for both trk and p75(NTR) remained unchanged at embryonic weeks 15 to 16 except for the addition of trk-ir and p75(NTR)-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 p75(NTR) 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 p75(NTR)-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 p75(NTR). 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.