DISSOCIATION OF P75 RECEPTORS AND NERVE GROWTH-FACTOR NEUROTROPHIC EFFECTS - LACK OF P75 IMMUNOREACTIVITY IN STRIATUM FOLLOWING PHYSICAL TRAUMA, EXCITOTOXICITY AND NGF ADMINISTRATION

While the function and regulation of the low affinity (p75) nerve grow th factor (NGF) receptor in the central nervous system (CNS) remains a mystery, one of the more intriguing observations involves its respons e to injury in the adult rat Striatum. Following mechanical injury to the striatum, a re-expression of striatal p75 receptors and mRNA purpo rtedly occurs (apparently mediated by elevations in NGF), thus reversi ng the natural loss of these phenotypic markers that is known to occur during development. This observation has important implications for u nderstanding both the regulation of NGF neurotrophic activity and the role of the p75 receptor, for it implies that the presence of this:rec eptor may be required for NGF trophic activity in the CNS. In an effor t to gain a greater understanding of the function and regulation of th e low affinity p75 NGF receptor, we performed a series of experiments to study the injury-induced, re-expression phenomenon in the striatum. In the first experiment, we duplicated the mechanical, cannula-induce d injury used in the original study. In a follow-up study, we exacerba ted that injury by infusing quinolinic acid directly into the striatum . In a third study, the mechanical injury was complemented with chroni c striatal infusions of NGF. In a final study, we examined striatal ti ssue from rats who had been protected from striatal quinolinic acid ne urotoxicity by administration of NGF. In no instance was the re-expres sion of, p75 striatal receptors observed, despite positive controls fo r (a) effective neural trauma, confirmed by histologic and immunocytoc hemical methods, (b) effective antibody staining, confirmed by appropr iate basal forebrain p75 immunoreactivity, and (c) effective biologica l activity of exogenous NGF, confirmed by hypertrophy of choline acety ltransferase (ChAT)-positive striatal neurons and protection of ChAT-p ositive striatal neurons against excitotoxicity. At least two importan t conclusions can be drawn from these studies: (1) the presence or ind uction of low affinity p75 receptors is not necessary, while the prese nce of constitutive high affinity tropomyosin related kinase (trk) NGF receptors seem sufficient for NGF trophic activity in the CNS, and (2 ) the variables necessary to induce re-expression of p75 striatal rece ptors in adult rats have not yet been elucidated and are apparently co mplex.