IMMUNOCYTOCHEMICAL LOCALIZATION OF TRKB IN THE CENTRAL-NERVOUS-SYSTEMOF THE ADULT-RAT

The TrkB family of transmembrane proteins serve as receptors for brain -derived neurotrophic factor (BDNF), neurotrophin (NT)-4/5, and possib ly NT-3, three members of the neurotrophin family of neurotrophic fact ors. In order to understand the potential roles played by these recept ors, we have examined the distribution of the TrkB receptor proteins i n the adult rat brain by using immunohistochemistry. Several different antisera, directed against either synthetic peptides corresponding to different regions of TrkB or a recombinant fusion protein comprising part of the extracellular domain, were generated. Each of these antise ra was directed to epitopes found on all known TrkB isoforms (both the tyrosine kinase-possessing isoform and the truncated kinase-lacking i soforms). In addition, a commercially available antibody to the intrac ellular domain of TrkB was also used. Widespread and distinct staining was observed on the surface of neuronal cell bodies, axons, and dendr ites in many structures, including the cerebral cortex, hippocampus, d entate gyrus, striatum, septal nuclei, substantia nigra, cerebellar Pu rkinje cells, brainstem and spinal motor neurons, and brainstem sensor y nuclei. Staining was also observed in the pia matter, on a subpopula tion of ependymal cells lining the cerebral ventricle wall, and other nonneuronal cells. The expression pattern of TrkB receptor protein sug gests that TrkB plays a broad role in the central nervous system. In a ddition, the detection of TrkB immunoreactivity on cell bodies and den drites is consistent with recent models suggesting that neurotrophins may be derived from presynaptic and/or autocrine sources in addition t o the classical postsynaptic target. (C) 1997 Wiley-Liss, Inc.