THE AGED MONKEY BASAL FOREBRAIN - RESCUE AND SPROUTING OF AXOTOMIZED BASAL FOREBRAIN NEURONS AFTER GRAFTS OF ENCAPSULATED CELLS SECRETING HUMAN NERVE GROWTH-FACTOR

Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricul ar transplants of polymer-encapsulated baby hamster kidney (BHK) fibro blasts that had been genetically modified to secrete human nerve growt h factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reducti ons in the number of choline acetyltransferase- (57-75%) and p75 NGF r eceptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsu lated hNGF-secreting cells display only a modest loss of choline acety ltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive se ptal neurons. Additionally, all monkeys receiving the hNGF-secreting i mplants, but none receiving control implants, displayed robust sprouti ng of cholinergic fibers within the septum ipsilateral to the transpla nt. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNG F. These data demonstrate that hNGF can provide trophic and tropic inf luences to aged primate basal forebrain neurons undergoing lesion-indu ced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.