Cellular and subcellular localization of nerve growth factor receptor-like immunoreactivity in the rat CNS.

The cellular actions of nerve growth factor (NGF) are known to be mediated through specific binding sites located on the cell membrane-bound NGF receptor (NGFr). Binding studies have revealed a high and a low affinity form of the NGFr although only the high affinity form is internalized. Most of the identified physiological effects of NGF appear to require internalization of the NGF-NGFr complex although details of subsequent events are still unclear. Since the relatively recent discovery that NGF exerts neurotrophic effects on cholinergic neurons of the rat basal forebrain, in addition to its previously known actions on sympathetic and sensory neurons of the peripheral nervous system, numerous morphological studies have localized the NGFr to such neurons in the forebrain. While the cellular localization of high affinity binding-sites using [(125)I]NGF radioautography has limitations of morphological resolution, NGFr immunoreactivity (IR) demonstrated by a monoclonal antibody, 192-IgG, may represent an epitope common to both low and high affinity forms of the NGFr and, possibly, one occurring in other related neurotrophic factor receptors. We have demonstrated NGFr-IR in neurons not only of the cholinergic basal forebrain nuclei but also of several other regions in the rat central nervous system, several of which are non-cholinergic. The use of colchicine to block the somatofugal transport of NGFr has revealed NGFr-IR in specific non-cholinergic neuronal populations where otherwise little or none is seen. These findings expand on the notion that NGF effects are not restricted to cholinergic neurons. Immunoelectron microscopy of nucleus basalis magnocellularis neurons has allowed identification of the subcellular sites of NGFr protein synthesis, modification, packaging and possible catabolism. We have also observed NGFr-IR within coated vesicles suggesting receptor internalization. Our ultrastructural observations demonstrate the utility of 192-IgG in studying the intracellular compartmentalization of NGFr reaction product and provide further evidence that 192-IgG labels an epitope common to both the low and high affinity NGFr.