IN-SITU HYBRIDIZATION DETECTION OF TRKA MESSENGER-RNA IN BRAIN - DISTRIBUTION, COLOCALIZATION WITH P75(NGFR) AND UP-REGULATION BY NERVE GROWTH-FACTOR

In situ hybridization techniques were used to examine the distribution and the nerve growth factor (NGF) regulation of trkA mRNA in the adul t rat brain in order to identify neurons in discrete regions of the br ain that may be NGF responsive. In agreement with previous studies, tr kA mRNA was detected within cells located in the medial septum (MS), d iagonal band of Broca (DBB), and caudate. trkA mRNA was also detected in many other regions of the brain, including the nucleus basalis of M eynert, substantia innominata, paraventricular nucleus of the thalamus , interpeduncular nucleus, prepositus hypoglossal nucleus, vestibular nuclei, raphe obscuris, cochlear nucleus, sensory trigeminal nuclei, a nd gigantocellular as well as perigigantocellular neurons in the medul lary reticular formation. By combining in situ hybridization detection of trkA mRNA with immunocytochemical detection of p75(NGFR), it was d etermined that the vast majority (> 90%) of the trkA mRNA-containing c ells detected in the MS and DBB also express p75(NGFR). Likewise, the vast majority of p75(NGFR)-IR cells detected in the MS and DBB express ed trkA mRNA. Intracerebroventricular infusions of NGF into the third ventricle adjacent to the preoptic area resulted in a 58% increase in relative cellular levels of trkA mRNA in the horizontal limb of the DB B. These data provide evidence that both p75(NGFR) and trkA are expres sed by NGF-responsive neurons in the MS and DBB. In addition, we note that areas that contained trkA mRNA and that also have been reported t o contain p75(NGFR) are areas where high-affinity NGF binding sites ha ve been observed autoradiographically, whereas areas that contain eith er trkA or p75(NGFR) alone are areas where no high-affinity NGF bindin g has been reported. Together, these findings suggest that both trkA a nd p75(NGFR) play an important role in the formation of high-affinity NGF receptors in brain and, furthermore, suggest that NGF may have phy siological effects within many regions of the brain outside of the bas al forebrain. (C) 1994 Wiley-Liss, Inc.