A low-affinity nerve growth factor receptor antibody is internalized and retrogradely transported selectively into...

The mechanism by which nerve growth factor transduces its signal in responsive cells is yet to be clearly defined. However, it has been suggested that the internalization of nerve growth factor, the first step in the retrograde flow of nerve growth factor, is a property of the high-affinity receptors, p140trkA. Here we show that when a monoclonal antibody (MC 192), which immunoprecipitates p75NGFR (the low-affinity 75,000 mol. wt nerve growth factor receptor protein) and not p140trkA, was administered into the dorsal hippocampal formation of the rats, it was internalized and retrogradely transported to the cell bodies residing in the medial septum-diagonal band complex. The topographic organization and the localization of these neurons containing retrogradely transported p75NGFR antibody were strikingly similar to those nerve cells immunostained for choline acetyltransferase in the immediately-adjacent section, indicating that the neurons which contained p75NGFR antibody were cholinergic neurons. A double-label immunocytochemistry confirmed this conclusion. On the other hand, none of the parvalbumin-positive GABAergic neurons contained retrogradely transported p75NGFR antibody. Moreover, in contrast to specific transport of p75NGFR antibody into cholinergic neurons, when wheat germ agglutinin-colloidal gold was injected into the hippocampus at the same levels, it was taken up and retrogradely transported into both choline acetyltransferase-positive cholinergic and parvalbumin-immunoreactive GABAergic neurons in the medial septum-diagonal band complex.