RETROGRADE DEGENERATION AND COLCHICINE PROTECTION OF BASAL FOREBRAIN CHOLINERGIC NEURONS FOLLOWING HIPPOCAMPAL INJECTIONS OF AN IMMUNOTOXINAGAINST THE P75 NERVE GROWTH-FACTOR RECEPTOR

Intracerebroventricular injection of 192 IgG antibody against the p75( LNGFR) rat low affinity nerve growth factor receptor conjugated with s aporin, a ribosome inactivating protein, has been shown to destroy the p75(LNGFR)-expressing cholinergic neurons of the basal forebrain. We injected this immunotoxin into the hippocampus and studied its retrogr ade effect upon the cholinergic neurons of the medial septum and the v ertical limb of the diagonal band of Broca. Seven days after injection , there was a nearly total depletion of cholinergic axons within the h ippocampus. This depletion was associated with a marked and significan t decrease in the number of cholinergic neurons of the ipsilateral med ial septum and the vertical limb of the diagonal band of Broca. At lon ger survival times, these changes were more pronounced. Parvalbumin-po sitive, GABAergic neurons within the same areas of the basal forebrain were not affected by immunotoxin injections. Injections of saporin al one had no effect upon cholinergic neurons. Simultaneous injection of colchicine with the immunotoxin resulted in a significant reduction of retrograde degeneration of cholinergic neurons and relative preservat ion of hippocampal cholinergic axons. These observations suggest that 192 IgG-saporin is transported retrogradely from the hippocampus to th e cholinergic neurons in the medial septum and the vertical limb of th e diagonal band of Broca and provide a model for retrograde degenerati on of basal forebrain cholinergic neurons following cortically based t oxic-pathologic processes. (C) 1997 IBRO.