TRKA-IMMUNOREACTIVE PROFILES IN THE CENTRAL-NERVOUS-SYSTEM - COLOCALIZATION WITH NEURONS CONTAINING P75 NERVE GROWTH-FACTOR RECEPTOR, CHOLINE-ACETYLTRANSFERASE, AND SEROTONIN

The present investigation used an antibody directed against the extrac ellular domain of the signal transducing nerve growth factor receptor, trkA, to reveal immunoreactive perikarya or fibers within the olfacto ry bulb and tubercle, cingulate cortex, nucleus accumbens, striatum, e ndopiriform nucleus, septal/diagonal band complex, nucleus basalis, hi ppocampal complex, thalamic paraventricular and reuniens nuclei, periv entricular hypothalamus, interpeduncular nucleus, mesencephalic nucleu s of the fifth nerve, dorsal nucleus of the lateral lemniscus, preposi tus hypoglossal nucleus, ventral cochlear nucleus, ventral lateral teg mentum, medial vestibular nucleus, spinal trigeminal nucleus oralis, n ucleus of the solitary tract, raphe nuclei, and spinal cord. Colocaliz ation experiments revealed that virtually all striatal trkA-immunoreac tive neurons (>99%) coexpressed choline acetyltransferase (ChAT) but n ot p75 nerve growth factor receptor (NGFR). Within the septal/diagonal band complex virtually all trkA neurons (>95%) coexpressed both ChAT and p75 NGFR. More caudally, dual stained sections revealed numerous t rkA/ChAT (>80%) and trkA/p75 NGFR (>95%) immunoreactive neurons within the nucleus basalis. In the brainstem, raphe serotonergic neurons (45 %) coexpressed trkA. Sections stained with a pan-trk antibody that rec ognizes primarily trkA, as well as trkB and trkC, labeled neurons with in all of these regions as well as within the hypothalamic arcuate, su pramammilary, and supraoptic nuclei, hippocampus, inferior and superio r colliculus, substantia nigra, ventral tegmental area of T'sai, and c erebellar Purkinje cells. Virtually all of these other regions with th e exception of the cerebellum also expressed pan-trk immunoreactivity in the monkey. The widespread expression of trkA throughout the centra l neural axis suggests that this receptor may play a role in signal tr ansduction mechanisms linked to NGF-related substances in cholinergic basal forebrain and noncholinergic systems. These findings suggest tha t pharmacological use of ligands for trkA could have beneficial effect s on the multiple neuronal systems that are affected in such disorders as Alzheimer's disease. (C) 1994 Wiiey-Liss, Inc.