Intracerebroventricular infusion of CHO5, a rat monoclonal antibody directed against mouse low-affinity nerve growth factor receptor (p75NTR), specifically labels basal forebrain cholinergic neurons in mouse brain.

Abstract

The finding that basal forebrain cholinergic cells are specifically endowed with the low-affinity nerve growth factor receptor p75NTR has been employed to develop a cholinergic immunotoxin in rats by covalently linking the monoclonal antibody 192IgG against the rat p75NTR with the cytotoxic protein saporin (192IgG-saporin). Following intracebroventricular application of 192IgG-saporin, the antibody conjugate is taken up into cholinergic cells via the p75NTR, retrogradely transported to the cell body, where saporin exerts cytotoxic action. The lack of an appropriate antibody directed against mouse p75NTR has been hampered the development of a mouse-specific cholinergic immunotoxin, which should be a useful tool to study effects of cortical cholinergic deficits on processing of amyloid precursor protein in transgenic mice with Alzheimer pathology. To develop an appropriate mouse-specific immunotoxin, a variety of antibodies directed against mouse p75NTR were tested. Using double labeling immunocytochemistry, the rat monoclonal antibody CHO5 against mouse p75NTR was found to label mouse basal forebrain neurons, which also demonstrated immunoreactivity for choline acetyltransferase and the high-affinity nerve growth factor receptor, TrkA. Intracerebroventricular infusion of CHO5 in mice resulted in an accumulation of the antibody in cholinergic cells within the basal forebrain, suggesting that CHO5 is a suitable candidate to develop a mouse-specific cholinergic immunotoxin.