192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat

Abstract

An immunotoxin (IT) composed of a monoclonal antibody to the nerve growth factor (NGF) receptor, 192 IgG, chemically linked to saporin, 192 IgG-saporin, was shown to selectively reduce forebrain choline acetyltransferase (ChAT) activity in the rat brain following intraventricular administration. In order to determine if the IT was killing NGF receptor-positive neurons in the CBF (rather than simply suppressing the cholinergic phenotype in these cells), a population of neurons in the nucleus basalis magnocellularis (NBM) was prelabeled by an intracortical injection of the neurotracer Fluoro-Gold (FG) 1 week before intraventricular injections of IT or control substances (reduced IT or phosphate-buffered saline). We found that there were very few double-labeled (i.e. FG-labeled and ChAT-positive) neurons remaining in the NBM of IT-treated animals. The absolute number of FG-labeled neurons in the NBM of IT-treated animals was reduced by a number similar to the counts of double-labeled neurons in the NBM of control animals. Our conclusion is that the IT is preferentially lethal to cholinergic neurons in the NBM. Due to its ability to selectively kill cholinergic neurons in the CBF and concomitantly spare noncholinergic neurons with similar morphology and projections, 192 IgG-saporin can be used to produce a selective model of CBF deficit in the rat.