TRK AND P75 NEUROTROPHIN RECEPTOR SYSTEMS IN THE DEVELOPING HUMAN BRAIN

The prenatal development of the neurons immunoreactive for high-affini ty 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) w as observed in the ventral cochlear, solitary, raphe, spinal trigemina l, and hypoglossal nuclei, as well as the vestibular complex and medul lary reticular formation. At this time point of gestation, p75(NTR)-im munoreactive (p75(NTR)-ir) staining was observed within these same reg ions plus the inferior olivary and ambiguus nuclei. At embryonic week 14, trk-ir neurons were seen within the subplate zone of the entorhina l cortex, basal forebrain, caudate nucleus, putamen, external segment of the globus pallidus, specific thalamic nuclei, lateral mammillary n ucleus, habenula nucleus, select brainstem nuclei, and the dentate nuc leus of cerebellum. At this gestational time point, p75(NTR)-ir neuron s 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 observe d within the corpus callosum. The staining pattern for both trk and p7 5(NTR) remained unchanged at embryonic weeks 15 to 16 except for the a ddition of trk-ir and p75(NTR)-ir within the cortical subplate zone, h ippocampus, and subthalamic nucleus. By embryonic week 18, trk-ir neur ons were widely expressed within mostly all thalamic nuclei. In contra st, trk-ir was no longer seen within the hypoglossal, cuneate, and gra cile nuclei at this time point. This staining pattern for trk and p75( NTR) remained virtually unchanged from embryonic weeks 19 to 20 and em bryonic weeks 16 to 20, respectively. From embryonic weeks 22 to 34, t he distribution of both trk-ir and p75(NTR)-ir neurons changed gradual ly. During this period, neurons in most thalamic and some brainstem nu clei became progressively immunonegative for trk, whereas neurons in t he neocortical subplate zone, corpus callosum, and hilar region of den tate gyrus gradually lost immunoreactivity for p75(NTR). These data de monstrate an important and complex role for both the high- (trk) and l ow-(p75) affinity neurotrophin receptors during the development of mul tiple neuronal systems in the human brain. (C) 1996 Wiley-Liss, Inc.