EFFECTS OF INTRAVENTRICULAR TRANSPLANTATION OF NGF-SECRETING CELLS ONCHOLINERGIC BASAL FOREBRAIN NEURONS AFTER PARTIAL IMMUNOLESION

The aim of the present study was to examine the effects of nerve growt h factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG-sapori n, Two weeks after intraventricular injections of 1.3 mu g of 192 IgG- saporin, about 50% of CBFNs were lost which was associated with 40-60% reductions of choline acetyltransferase (ChAT) and high-affinity chol ine uptake (HACU) activities throughout the basal forebrain cholinergi c system, Two groups of lesioned animals received intraventricular tra nsplantations of mouse 3T3 fibroblasts retrovirally transfected with e ither the rat NGF gene (3T3(NGF+)) or the retrovirus alone (3T3(NGF-)) and were sacrificed eight weeks later, In vivo production of NGF by 3 T3(NGF+) cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples, Both ChAT a nd HACU activities returned to normal control levels in the basal fore brain and cortex after 3T3(NGF+) transplants, whereas no recovery was observed in 3T3(NGF-) transplanted animals, There was a 25% increase i n the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments, Acetylcholin esterase (AChE) histochemistry revealed that the optical density of AC hE-positive fibers in the cerebral cortex and hippocampus were reduced by about 60% in immunolesioned rats which were completely restored by 3T3(NGF+) grafts, In addition, decreases in growth-associated protein (GAP)-43 immunoreactivity after immunolesion and increases in synapto physin immunoreactivity after 3T3(NGF+) grafts were observed in the hi ppocampus, Our results further confirm the notion that transfected NGF -secreting cells are useful in long-term in vivo NGF treatment and NGF can upregulate CBFN function, They also highly suggest that NGF induc es terminal sprouting from remaining CBFNs. (C) 1996 Wiley-Liss, Inc.