Distribution and relative density of p75 nerve growth factor receptors in the rat brain as a function of age and treatment with antibodies to nerve growth factor.

It is clear that nerve growth factor (NGF) has a role in the central nervous system. In order to begin to determine the possible roles of NGF in the CNS, neonatal rats were given daily subcutaneous injections of antibodies to NGF (ANTI-NGF) beginning at birth for a period of one month. By utilizing the monoclonal antibody, 192-IgG, which recognizes the p75 NGF receptor (NGFR), and standard immunohistochemical techniques we have localized p75 NGFR in variously aged ANTI-NGF-treated animals and compared the anatomic localization and relative density of the p75 NGFR immunoreactive (p75 NGFR-I) regions to same age untreated and preimmune sera-treated littermates. We confirm previously reported localizations of p75 NGFR-I in the rat brain. In addition, we demonstrate that p75 NGFR-I levels of ANTI-NGF-treated rats found in the molecular, the granular and the Purkinje cell layers of the cerebellum, the vestibular nuclei, the spinal tract of V and the cochlear nuclei remain at lower concentrations compared to same-age control animals. We also demonstrate that p75 NGFR-I levels in the basal nucleus approaches background levels after ANTI-NGF treatment. We hypothesize that ANTI-NGF biologically inactivates NGF, which over a period of 30 days results in decreased p75 NGFR-I. These results are consistent with neuronal loss in these regions following ANTI-NGF treatment. Furthermore, the immunological methods used to produce the specific deficits in the present study may have broader implications with respect to usefulness as a method for determining the dependency of CNS neuronal populations for a putative neurotrophic factor and as a method for the development of models of neurodegenerative diseases.